CLINICAL STUDIES - INDEPENDENT INGREDIENT REVIEW

There are a vast number of clinical studies over the last few decades that have shown the effectiveness of the ingredients found in VitaBack. Our clinical research team has compiled several of these studies with the results so that you can find out for yourself that the ingredients in VitaBack can help reduce back and neck pain*.

Vitamin D (Cholecalciferol) CLINICAL STUDIES

Vitamin D deficiency and chronic low back pain in Saudi Arabia

Vitamin D deficiency and chronic low back pain in Saudi Arabia.

Al Faraj S, Al Mutairi K. Vitamin D deficiency and chronic low back pain in Saudi Arabia. Spine (Phila Pa 1976). 2003 Jan 15;28(2):177-9. PubMed PMID: 12544936.

To investigate the contribution of vitamin D deficiency as a cause for idiopathic chronic low back pain, to find a simple and sensitive test for screening patients with low back pain for vitamin D deficiency, and to determine the correlation between the vitamin deficiency and pain. Findings showed that 83% of the study patients (n = 299) had an abnormally low level of vitamin D before treatment with vitamin D supplements. After treatment, clinical improvement in symptoms was seen in all the groups that had a low level of vitamin D, and in 95% of all the patients (n = 341). Vitamin D deficiency is a major contributor to chronic low back pain in areas where vitamin D deficiency is endemic. Screening for vitamin D deficiency and treatment with supplements should be mandatory in this setting. Measurement of serum 25-OH cholecalciferol is sensitive and specific for detection of vitamin D deficiency, and hence for presumed osteomalacia in patients with chronic low back pain.

Vitamin D supplementation for patients with chronic pain

Vitamin D supplementation for patients with chronic pain

Kragstrup TW. Vitamin D supplementation for patients with chronic pain. Scandinavian Journal of Primary Health Care. 2011;29(1):4-5. doi:10.3109/02813432.2010.530738.

A study in a previous issue of the Scandinavian Journal of Primary Health Care (SJPHC) adds to the growing list of publications on vitamin D as a possible treatment for chronic pain. It describes a high prevalence of hypovitaminosis D in patients with non-specific musculoskeletal pain, headache, and fatigue. The conclusion is that general practitioners should maintain awareness of hypovitaminosis D in these patients. The authors are, however, aware that firm conclusions regarding cause and effect cannot be based on a cross-sectional study, which leaves plenty of room for confounding. Vitamin D supply is defined by sun exposure and dietary intake, which may be affected by work, economy, culture, diseases etc. Similarly, chronic pain may be affected by work, economy, culture, diseases etc. It seems reasonable to use vitamin D supplementation (with or without previous measurement of the vitamin D status) with up to 50 μg (2.000 IU) daily for patients with chronic pain. The supplement may not be a cure for the pain, but the study in the SJPHC demonstrates that low levels of vitamin D are common in this group of patients. The treatment is cheap, relatively safe, and there is emerging evidence that vitamin D supplementation has positive effects on public health. Underlying conditions causing the chronic pain should be diagnosed irrespective of vitamin D status.

Vitamin D Deficiency and Pain: Clinical Evidence of Low Levels of Vitamin D and Supplementation in Chronic Pain States

Vitamin D Deficiency and Pain: Clinical Evidence of Low Levels of Vitamin D and Supplementation in Chronic Pain States

Shipton EE, Shipton EA. Vitamin D Deficiency and Pain: Clinical Evidence of Low Levels of Vitamin D and Supplementation in Chronic Pain States. Pain and Therapy. 2015;4(1):67-87. doi:10.1007/s40122-015-0036-8.

A number of studies suggest a link between low levels of 25-hydroxy vitamin D and incidence of acute and chronic pain. Clinical studies of vitamin D supplementation in patients with known vitamin D deficiency have shown mixed results in improving pain scores. There remains a growing body of both clinical and laboratory evidence pointing to a potential relationship between low levels of 25-hydroxy vitamin D and a variety of chronic pain states. More focused research involving large RCTs is necessary.

Vitamin D Deficiency, Prevention and Treatment

Vitamin D Deficiency, Prevention and Treatment

Iraj B, Ebneshahidi A, Askari G. Vitamin D Deficiency, Prevention and Treatment. International Journal of Preventive Medicine. 2012;3(10):733-736.

Case Study Result: The serum of 25 (OH) D was 42 ng/ml and the PTH was 70 Pg/ml. As it is known, the secondary hyperparathyroidism due to vitamin D deficiency improves after 6-12 months of treatment with vitamin D. Therefore, the serum PTH level in this patient is not worrisome. Therefore, the maintenance therapy in this patient continued and after 3 months of the treatment the patient reported sense of wellbeing and the low back pain and the throbbing bone pain totally resolved.

Vitamin D Supplementation in Patients with Chronic Low Back Pain: An Open Label, Single Arm Clinical Trial

"Vitamin D Supplementation in Patients with Chronic Low Back Pain: An Open Label, Single Arm Clinical Trial.

Ghai B, Bansal D, Kanukula R, Gudala K, Sachdeva N, Dhatt SS, Kumar V. Vitamin D Supplementation in Patients with Chronic Low Back Pain: An Open Label, Single Arm Clinical Trial. Pain Physician. 2017 Jan-Feb;20(1):E99-E105. PubMed PMID:28072801.

Vitamin-D deficiency may possibly be related to chronic low back pain (CLBP). The study is aimed to assess the impact of vitamin-D supplementation on pain intensity, functional disability, and vitamin-D levels in patients with CLBP. Vitamin-D supplementation in deficient CLBP patients may lead to improvement in pain intensity and functional ability apart from normalization of the levels. Future controlled clinical trials are required to confirm the hypothesis."


Vitamin B12 (Methylcobalamin) CLINICAL STUDIES
Vitamin B12 in low back pain: a randomised, double-blind, placebo-controlled study.

Vitamin B12 in low back pain: a randomised, double-blind, placebo-controlled study.

Mauro GL, Martorana U, Cataldo P, Brancato G, Letizia G. Vitamin B12 in low back pain: a randomised, double-blind, placebo-controlled study. Eur Rev Med Pharmacol Sci. 2000 May-Jun;4(3):53-8. PubMed PMID: 11558625.

The objective of this double-blind randomised, placebo-controlled study was to examine the efficacy and safety intramuscular vitamin B12 (Tricortin 1000) in the treatment of low back pain in patients with mechanical or irritative lumbago. Both treatment groups experienced a sharp decrease in pain and disability. However, comparison between groups at the end of the treatment period showed a statistically significant difference in favour of the active treatment both for VAS and DQ (p < 0.0001 and p < 0.0002, respectively). Consumption of paracetamol proved significantly higher in the placebo group than in the active treatment (p < 0.0001). The efficacy and safety of parenteral Vitamin B12 in alleviating low back pain and related disability and in decreasing the consumption of paracetamol was confirmed in patients with no signs of nutritional deficiency.

The efficacy and safety of intramuscular injections of methylcobalamin in patients with chronic nonspecific low back pain: a randomised controlled trial.

The efficacy and safety of intramuscular injections of methylcobalamin in patients with chronic nonspecific low back pain: a randomised controlled trial.

Chiu CK, Low TH, Tey YS, Singh VA, Shong HK. The efficacy and safety of intramuscular injections of methylcobalamin in patients with chronic nonspecific low back pain: a randomised controlled trial. Singapore Med J. 2011 Dec;52(12):868-73. PubMed PMID: 22159928.

Chronic, nonspecific low back pain is a difficult ailment to treat and poses an economic burden in terms of medical expenses and productivity loss. The aim of this study was to determine the efficacy and safety of intramuscular metylcobalamin in the treatment of chronic nonspecific low back pain. Intramuscular methylcobalamin is both an effective and safe method of treatment for patients with nonspecific low back pain, both singly or in combination with other forms of treatment.

Methylcobalamin: A Potential Vitamin of Pain Killer

Methylcobalamin: A Potential Vitamin of Pain Killer

Zhang M, Han W, Hu S, Xu H. Methylcobalamin: A Potential Vitamin of Pain Killer. Neural Plasticity. 2013;2013:424651. doi:10.1155/2013/424651.

Methylcobalamin (MeCbl), the activated form of vitamin B12, has been used to treat some nutritional diseases and other diseases in clinic, such as Alzheimer's disease and rheumatoid arthritis. As an auxiliary agent, it exerts neuronal protection by promoting regeneration of injured nerves and antagonizing glutamate-induced neurotoxicity. Recently several lines of evidence demonstrated that MeCbl may have potential analgesic effects in experimental and clinical studies. For example, MeCbl alleviated pain behaviors in diabetic neuropathy, low back pain and neuralgia. MeCbl improved nerve conduction, promoted the regeneration of injured nerves, and inhibited ectopic spontaneous discharges of injured primary sensory neurons. This review aims to summarize the analgesic effect and mechanisms of MeCbl at the present.

B complex vitamins for analgesic therapy

B complex vitamins for analgesic therapy

Gazoni, Fernanda Martins, Malezan, William Rafael, & Santos, Fânia Cristina. (2016). B complex vitamins for analgesic therapy. Revista Dor, 17(1), 52-56. https://dx.doi.org/10.5935/1806-0013.20160013

The B complex vitamins have been used as single therapy or combined to other drugs, such as anti-inflammatory drugs, in different clinical situations, such as degenerative spinal diseases, rheumatologic diseases, polyneuropathies and in different postoperative situations. This study aimed at identifying in the scientific literature most recent evidences of the use of B complex vitamins as analgesic therapy and at describing clinical situations where their analgesic action could be observed. Existing studies, although scarce and heterogeneous, have shown that B complex vitamins have analgesic effect. They are considered safe and have low cost and have shown to be a good option as adjuvant analgesic therapy.


Magnesium Bisglycinate Chelate CLINICAL STUDIES
Supplementation with alkaline minerals reduces symptoms in patients with chronic low back pain

Supplementation with alkaline minerals reduces symptoms in patients with chronic low back pain.

Vormann J, Worlitschek M, Goedecke T, Silver B. Supplementation with alkaline minerals reduces symptoms in patients with chronic low back pain. J Trace Elem Med Biol. 2001;15(2-3):179-83. PubMed PMID: 11787986.

The cause of low back pain is heterogeneous, it has been hypothesised that a latent chronic acidosis might contribute to these symptoms. It was tested whether a supplementation with alkaline minerals would influence symptoms in patients with low back pain symptoms. In an open prospective study 82 patients with chronic low back pain received daily 30 g of a lactose based alkaline multimineral supplement (Basica) over a period of 4 weeks in addition to their usual medication. Pain symptoms were quantified with the "Arhus low back pain rating scale" (ARS). Mean ARS dropped highly significant by 49% from 41 to 21 points after 4 weeks supplemention. In 76 out of 82 patients a reduction in ARS was achieved by the supplementation. Total blood buffering capacity was significantly increased from 77.69 +/- 6.79 to 80.16 +/- 5.24 mmol/L (mean +/- SEM, n = 82, p < 0.001) and also blood pH rose from 7.456 +/- 0.007 to 7.470 +/- 0.007 (mean +/- SEM, n = 75, p < 0.05). Only intracellular magnesium increased by 11% while other intracellular minerals were not significantly changed in sublingual tissue as measured with the EXA-test. Plasma concentrations of potassium, calcium, iron, copper, and zinc were within the normal range and not significantly influenced by the supplementation. Plasma magnesium was slightly reduced after the supplemenation (-3%, p < 0.05). The results show that a disturbed acid-base balance may contribute to the symptoms of low back pain. The simple and safe addition of an alkaline multimineral preparate was able to reduce the pain symptoms in these patients with chronic low back pain.

Magnesium-oral supplementation to reduce Pain in patients with severe Peripheral arterial occlusive disease: the MAG-PAPER randomized clinical trial protocol

MAGnesium-oral supplementation to reduce PAin in patients with severe PERipheral arterial occlusive disease: the MAG-PAPER randomised clinical trial protocol

Venturini MA, Zappa S, Minelli C, et al. MAGnesium-oral supplementation to reduce PAin in patients with severe PERipheral arterial occlusive disease: the MAG-PAPER randomised clinical trial protocol. BMJ Open. 2015;5(12):e009137. doi:10.1136/bmjopen-2015-009137.

Magnesium exerts analgaesic effects in several animal pain models, as well as in patients affected by acute postoperative pain and neuropathic chronic pain. There is no evidence that magnesium can modulate pain in patients with peripheral arterial occlusive disease (PAOD). We describe the protocol of a single-centre randomised double-blind clinical trial aimed at assessing the efficacy of oral magnesium supplementation in controlling severe pain in patients with advanced PAOD.


Zinc Glycinate Chelate (TRAACS) CLINICAL STUDIES
Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit

Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit

Nozaki C, Vergnano AM, Filliol D, et al. Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit. Nature neuroscience. 2011;14(8):1017-1022. doi:10.1038/nn.2844.

Zinc is abundant in the central nervous system and regulates pain, but the underlying mechanisms are unknown. In vitro studies have shown that extracellular zinc modulates a plethora of signaling membrane proteins, including NMDA receptors containing the NR2A subunit, which display exquisite zinc sensitivity. We created NR2A-H128S knock-in mice to investigate whether Zn2+–NR2A interaction influences pain control. In these mice, high-affinity (nanomolar) zinc inhibition of NMDA currents was lost in the hippocampus and spinal cord. Knock-in mice showed hypersensitivity to radiant heat and capsaicin, and developed enhanced allodynia in inflammatory and neuropathic pain models. Furthermore, zinc-induced analgesia was completely abolished under both acute and chronic pain conditions. Our data establish that zinc is an endogenous modulator of excitatory neurotransmission in vivo and identify a new mechanism in pain processing that relies on NR2A NMDA receptors. The study also potentially provides a molecular basis for the pain-relieving effects of dietary zinc supplementation.


Manganese Bisglycinate Chelate (TRAACS) CLINICAL STUDIES
Retooling Manganese(III) Porphyrin-Based Peroxynitrite Decomposition Catalysts for Selectivity and Oral Activity: A Potential New Strategy for Treating Chronic Pain

Retooling Manganese(III) Porphyrin-Based Peroxynitrite Decomposition Catalysts for Selectivity and Oral Activity: A Potential New Strategy for Treating Chronic Pain

Rausaria S, Ghaffari MME, Kamadulski A, et al. Retooling Manganese(III) Porphyrin-Based Peroxynitrite Decomposition Catalysts for Selectivity and Oral Activity: A Potential New Strategy for Treating Chronic Pain. Journal of medicinal chemistry. 2011;54(24):8658-8669. doi:10.1021/jm201233r.

Redox-active metalloporphyrins represent the most well characterized class of catalysts capable of attenuating oxidative stress in vivo through the direct interception and decomposition of superoxide and peroxynitrite. While many interesting pharmacological probes have emerged from these studies, few catalysts have been developed with pharmaceutical properties in mind. Herein we describe our efforts to identify new Mn(III)-porphyrin systems with enhanced membrane solubilizing properties. To this end seven new Mn(III)-tetracyclohexenylporphyin (TCHP) analogues 7, 10, 12, 15, 16a–c have been prepared in which the beta-fused cyclohexenyl rings provide a means to shield the charged metal center from the membrane during passive transport. Compounds 7, 15, and 16a–c have been shown to be orally active and potent analgesics in a model of carrageenan-induced thermal hyperalgesia. In addition oral administration of compound 7 (10–100 mg/kg, n = 5) has been shown to dose dependently reverse mechano-allodynia in the CCI model of chronic neuropathic pain.


Glucosamine (Glucosamine Sulfate Complex) CLINICAL STUDIES
Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: Biochemical rationale and case report

Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: Biochemical rationale and case report

Van Blitterswijk WJ, van de Nes JC, Wuisman PI. Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: Biochemical rationale and case report. BMC Complementary and Alternative Medicine. 2003;3:2. doi:10.1186/1472-6882-3-2.

Glucosamine and chondroitin sulfate preparations are widely used as food supplements against osteoarthritis, but critics are skeptical about their efficacy, because of the lack of convincing clinical trials and a reasonable scientific rationale for the use of these nutraceuticals. Most trials were on osteoarthritis of the knee, while virtually no documentation exists on spinal disc degeneration. The purpose of this article is to highlight the potential of these food additives against cartilage degeneration in general, and against symptomatic spinal disc degeneration in particular, as is illustrated by a case report. The water content of the intervertebral disc is a reliable measure of its degeneration/ regeneration status, and can be objectively determined by Magnetic Resonance Imaging (MRI) signals. The case suggests that long-term glucosamine and chondroitin sulfate intake may counteract symptomatic spinal disc degeneration, particularly at an early stage. However, definite proof requires well-conducted clinical trials with these food supplements, in which disc de-/regeneration can be objectively determined by MRI. A number of biochemical reasons (that mechanistically need to be further resolved) explain why these agents may have cartilage structure- and symptom-modifying effects, suggesting their therapeutic efficacy against osteoarthritis in general.

Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids

Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids

Jerosch J. Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids. International Journal of Rheumatology. 2011;2011:969012. doi:10.1155/2011/969012.

Osteoarthritis (OA) is a degenerative joint disease that is characterized by increasing loss of cartilage, remodeling of the periarticular bone, and inflammation of the synovial membrane. Besides the common OA therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the treatment with chondroprotectives, such as glucosamine sulfate, chondroitin sulfate, hyaluronic acid, collagen hydrolysate, or nutrients, such as antioxidants and omega-3 fatty acids is a promising therapeutic approach. Numerous clinical studies have demonstrated that the targeted administration of selected micronutrients leads to a more effective reduction of OA symptoms, with less adverse events. Their chondroprotective action can be explained by a dual mechanism: (1) as basic components of cartilage and synovial fluid, they stimulate the anabolic process of the cartilage metabolism; (2) their anti-inflammatory action can delay many inflammation-induced catabolic processes in the cartilage. These two mechanisms are able to slow the progression of cartilage destruction and may help to regenerate the joint structure, leading to reduced pain and increased mobility of the affected joint.


Hydrolyzed Collagen CLINICAL STUDIES
24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain

24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain.

Clark KL, Sebastianelli W, Flechsenhar KR, Aukermann DF, Meza F, Millard RL, Deitch JR, Sherbondy PS, Albert A. 24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Curr Med Res Opin. 2008 May;24(5):1485-96. doi: 10.1185/030079908X291967 . Epub 2008 Apr 15. PubMed PMID: 18416885.

Collagen hydrolysate is a nutritional supplement that has been shown to exert an anabolic effect on cartilage tissue. Its administration appears beneficial in patients with osteoarthritis. This was the first clinical trial of 24-weeks duration to show improvement of joint pain in athletes who were treated with the dietary supplement collagen hydrolysate. The results of this study have implications for the use of collagen hydrolysate to support joint health and possibly reduce the risk of joint deterioration in a high-risk group. Despite the study's size and limitations, the results suggest that athletes consuming collagen hydrolysate can reduce parameters (such as pain) that have a negative impact on athletic performance. Future studies are needed to support these findings.

Role of collagen hydrolysate in bone and joint disease

Role of collagen hydrolysate in bone and joint disease.

Moskowitz RW. Role of collagen hydrolysate in bone and joint disease. Semin Arthritis Rheum. 2000 Oct;30(2):87-99. PubMed PMID: 11071580.

To review the current status of collagen hydrolysate in the treatment of osteoarthritis and osteoporosis. Collagen hydrolysate is of interest as a therapeutic agent of potential utility in the treatment of osteoarthritis and osteoporosis. Its high level of safety makes it attractive as an agent for long-term use in these chronic disorders.

Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders: a review of the literature

Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders: a review of the literature.

Bello AE, Oesser S. Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders: a review of the literature. Curr Med Res Opin. 2006 Nov;22(11):2221-32. Review. PubMed PMID: 17076983.

There is a need for an effective treatment for the millions of people in the United States with osteoarthritis (OA), a degenerative joint disease. The demand for treatments, both traditional and non-traditional, will continue to grow as the population ages. According to published research, orally administered collagen hydrolysate has been shown to be absorbed intestinally and to accumulate in cartilage. Collagen hydrolysate ingestion stimulates a statistically significant increase in synthesis of extracellular matrix macromolecules by chondrocytes (p < 0.05 compared with untreated controls). These findings suggest mechanisms that might help patients affected by joint disorders such as OA. Four open-label and three double-blind studies were identified and reviewed; although many of these studies did not provide key information--such as the statistical significance of the findings--they showed collagen hydrolysate to be safe and to provide improvement in some measures of pain and function in some men and women with OA or other arthritic conditions. A growing body of evidence provides a rationale for the use of collagen hydrolysate for patients with OA. It is hoped that ongoing and future research will clarify how collagen hydrolysate provides its clinical effects and determine which populations are most appropriate for treatment with this supplement.


Bromelain CLINICAL STUDIES
Properties and Therapeutic Application of Bromelain: A Review

Properties and Therapeutic Application of Bromelain: A Review

Pavan R, Jain S, Shraddha, Kumar A. Properties and Therapeutic Application of Bromelain: A Review. Biotechnology Research International. 2012;2012:976203. doi:10.1155/2012/976203.

Bromelain belongs to a group of protein digesting enzymes obtained commercially from the fruit or stem of pineapple. Fruit bromelain and stem bromelainare prepared differently and they contain different enzymatic composition. “Bromelain” refers usually to the “stem bromelain.” Bromelain is a mixture of different thiol endopeptidases and other components like phosphatase, glucosidase, peroxidase, cellulase, escharase, and several protease inhibitors. In vitro and in vivo studies demonstrate that bromelain exhibits various fibrinolytic, antiedematous, antithrombotic, and anti-inflammatory activities. Bromelain is considerably absorbable in the body without losing its proteolytic activity and without producing any major side effects. Bromelain accounts for many therapeutic benefits like the treatment of angina pectoris, bronchitis, sinusitis, surgical trauma, and thrombophlebitis, debridement of wounds, and enhanced absorption of drugs, particularly antibiotics. It also relieves osteoarthritis, diarrhea, and various cardiovascular disorders. Bromelain also possesses some anticancerous activities and promotes apoptotic cell death. This paper reviews the important properties and therapeutic applications of bromelain, along with the possible mode of action.

Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies

Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies

Brien S, Lewith G, Walker A, Hicks SM, Middleton D. Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies. Evidence-based Complementary and Alternative Medicine. 2004;1(3):251-257. doi:10.1093/ecam/neh035.

Bromelain, an extract from the pineapple plant, has been demonstrated to show anti-inflammatory and analgesic properties and may provide a safer alternative or adjunctive treatment for osteoarthritis. All previous trials, which have been uncontrolled or comparative studies, indicate its potential use for the treatment of osteoarthritis. This paper reviews the mechanism of its putative therapeutic actions, those clinical trials that have assessed its use in osteoarthritis to date, as well as considering the safety implications of this supplement for osteoarthritis and reviewing the evidence to date regarding the dosage for treating this condition. The data available at present indicate the need for trials to establish the efficacy and optimum dosage for bromelain and the need for adequate prospective adverse event monitoring in such chronic conditions as osteoarthritis.

A complex of three natural anti-inflammatory agents provides relief of osteoarthritis pain

A complex of three natural anti-inflammatory agents provides relief of osteoarthritis pain.

Conrozier T, Mathieu P, Bonjean M, Marc JF, Renevier JL, Balblanc JC. A complex of three natural anti-inflammatory agents provides relief of osteoarthritis pain. Altern Ther Health Med. 2014 Winter;20 Suppl 1:32-7. PubMed PMID: 24473984.

Devil's claw (Harpagophytum procumbens), turmeric (Curcuma longa), and bromelain are nutraceuticals that have demonstrated anti-inflammatory and analgesic properties and may be potential solutions in the treatment of acute or chronic joint pain. Their analgesic effect, however, is generally considered mild to moderate, and the relevance of their clinical use remains subject to discussion. The aim of the study was to evaluate the clinical relevance of the efficacy of a marketed complex of 3 plant extracts-H procumbens, C longa, and bromelain (AINAT, 650 mg)-in the treatment of degenerative joint pain The improvement of joint pain was clinically relevant in patients treated with AINAT for both acute and chronic OA pain. Considering its excellent tolerance profile, the tested complex of 3 plant extracts with antiinflammatory properties may be a valuable and safe alternative to NSAIDs in patients suffering from degenerative joint diseases.


Hyaluronic acid (from Sodium Hyaluronate) CLINICAL STUDIES
Intraarticular hyaluronic acid versus glucocorticoid injections for nonradicular pain in the lumbar spine

Intraarticular hyaluronic acid versus glucocorticoid injections for nonradicular pain in the lumbar spine.

Fuchs S, Erbe T, Fischer HL, Tibesku CO. Intraarticular hyaluronic acid versus glucocorticoid injections for nonradicular pain in the lumbar spine. J Vasc Interv Radiol. 2005 Nov;16(11):1493-8. PubMed PMID: 16319156.

To investigate the efficacy and safety of intraarticular sodium hyaluronate (SH) compared with intraarticular glucocorticoids (triamcinolone acetonide; TA) in the treatment of chronic nonradicular lumbar pain. Patients reported lasting pain relief, better function, and improved quality of life with both treatments. Mann-Whitney analyses of the patient questionnaires (RMQ, ODQ, and LBOS) very consistently showed that SH is not inferior to TA. In addition, the efficacy of SH was largely comparable with that of TA on the VAS and SF-36. No adverse effects were reported after administration of the test products. The intraarticular treatment of facet joints (levels S1-L5, L5-L4, and L4-L3) with SH in patients with chronic nonradicular pain in the lumbar spine resulted in a marked reduction in pain with improved function and better quality of life, which was at least equal to the effect of a course of TA injections. SH-treated patients showed greater benefits in the long term. Intraarticular SH is a very promising new option for the treatment of patients with chronic nonradicular lumbar symptoms.

Effectiveness and utility of hyaluronic acid in osteoarthritis

Effectiveness and utility of hyaluronic acid in osteoarthritis

Migliore A, Procopio S. Effectiveness and utility of hyaluronic acid in osteoarthritis. Clinical Cases in Mineral and Bone Metabolism. 2015;12(1):31-33. doi:10.11138/ccmbm/2015.12.1.031.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by pain and progressive functional limitation. Viscosupplementation with intra-articular hyaluronic acid is a treatment option in knee OA that is included in the professional guidelines for treatment of this joint disease, but potentially should apply to all synovial joints in order to reduce pain and improve joint lubrication. Exogenous HA can enhance chondrocyte HA synthesis, prevent the degradation of cartilage and promote its regeneration. Moreover it can reduce the production of proinflammatory mediators and matrix metalloproteinases involved in OA pathogenesis. This mini review highlights the evidence of hyaluronic acid in reducing osteoarthritis symptoms and structural damage, as well as its ability to delay prosthetic surgery. Viscosupplementation should be considered as a long-term therapy.

The effectiveness of hyaluronic acid intra-articular injections in managing osteoarthritic knee pain

The effectiveness of hyaluronic acid intra-articular injections in managing osteoarthritic knee pain

Trigkilidas D, Anand A. The effectiveness of hyaluronic acid intra-articular injections in managing osteoarthritic knee pain. Annals of The Royal College of Surgeons of England. 2013;95(8):545-551. doi:10.1308/003588413X13629960049432.

Knee osteoarthritis (OA) is a common and progressive joint disease. Treatment options for knee OA vary from simple analgesia in mild cases to knee replacement for advanced disease. Knee pain due to moderate OA can be targeted with intra-articular injections. Steroid injections have been used widely in managing acute flare-ups of the disease. In recent years, viscosupplementation has been used as a therapeutic modality for the management of knee OA. The principle of viscosupplementation is based on the physiological properties of the hyaluronic acid (HA) in the synovial joint. Despite a sound principle and promising in vitro studies, clinical studies have been less conclusive on the effectiveness of HA in managing osteoarthritic knee pain. The aim of this systematic review was to assess the effectiveness of HA intra-articular injections in the management of osteoarthritic knee pain. HA intra-articular injections have a modest effect on early to moderate knee OA. The effect peaks at around 6–8 weeks following administration, with a doubtful effect at 6 months.


Chondroitin Sulfate CLINICAL STUDIES
Effectiveness and safety of Glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of osteoarthritis of the knee

Effectiveness and safety of Glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of osteoarthritis of the knee

Zeng C, Wei J, Li H, et al. Effectiveness and safety of Glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of osteoarthritis of the knee. Scientific Reports. 2015;5:16827. doi:10.1038/srep16827.

This study aimed to investigate the effectiveness and safety of glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of knee osteoarthritis (OA). PubMed, Embase and Cochrane Library were searched through from inception to February 2015. A total of 54 studies covering 16427 patients were included. Glucosamine plus chondroitin, glucosamine alone, and celecoxib were all more effective than placebo in pain relief and function improvement. Specifically, celecoxib is most likely to be the best treatment option, followed by the combination group. All treatment options showed clinically significant improvement from baseline pain, but only glucosamine plus chondroitin showed clinically significant improvement from baseline function. In terms of the structure-modifying effect, both glucosamine alone and chondroitin alone achieved a statistically significant reduction in joint space narrowing. Although no significant difference was observed among the five options with respect to the three major adverse effects (withdrawal due to adverse events, serious adverse events and the number of patients with adverse events), the additional classical meta-analysis showed that celecoxib exhibited a higher rate of gastrointestinal adverse effect comparing with the placebo group. The present study provided evidence for the symptomatic efficacy of glucosamine plus chondroitin in the treatment of knee OA.

Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids

Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids

Jerosch J. Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids. International Journal of Rheumatology. 2011;2011:969012. doi:10.1155/2011/969012.

Osteoarthritis (OA) is a degenerative joint disease that is characterized by increasing loss of cartilage, remodeling of the periarticular bone, and inflammation of the synovial membrane. Besides the common OA therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the treatment with chondroprotectives, such as glucosamine sulfate, chondroitin sulfate, hyaluronic acid, collagen hydrolysate, or nutrients, such as antioxidants and omega-3 fatty acids is a promising therapeutic approach. Numerous clinical studies have demonstrated that the targeted administration of selected micronutrients leads to a more effective reduction of OA symptoms, with less adverse events. Their chondroprotective action can be explained by a dual mechanism: (1) as basic components of cartilage and synovial fluid, they stimulate the anabolic process of the cartilage metabolism; (2) their anti-inflammatory action can delay many inflammation-induced catabolic processes in the cartilage. These two mechanisms are able to slow the progression of cartilage destruction and may help to regenerate the joint structure, leading to reduced pain and increased mobility of the affected joint.


L-proline CLINICAL STUDIES
Alterations of amino acid metabolism in osteoarthritis: its implications for nutrition and health

Alterations of amino acid metabolism in osteoarthritis: its implications for nutrition and health.

Li Y, Xiao W, Luo W, Zeng C, Deng Z, Ren W, Wu G, Lei G. Alterations of amino acid metabolism in osteoarthritis: its implications for nutrition and health. Amino Acids. 2016 Apr;48(4):907-14. doi: 10.1007/s00726-015-2168-x. Epub 2016 Jan 14. Review. PubMed PMID: 26767374.

Osteoarthritis (OA) is a common form of arthritis in humans. It has long been regarded as a non-inflammatory disease, but a degree of inflammation is now recognized as being a vital inducer of subpopulation of OA. Besides inflammation, the establishment and development of OA are associated with alterations in metabolism and profiles of amino acids (AA), including glutamate- and arginine-family AA as well as their related metabolites (e.g., creatinine, hydroxyproline, γ-aminobutyrate, dimethylarginines and homoarginine). Functional AA (e.g., glutamine, arginine, glutamate, glycine, proline, and tryptophan) have various benefits (i.e., anti-inflammation and anti-oxidation) in treatment of inflammation-associated diseases, including OA. Thus, these AA have potential as immunomodulatory nutrients for patients with inflammation-induced OA.


L-glutamine CLINICAL STUDIES
Alterations of amino acid metabolism in osteoarthritis: its implications for nutrition and health

Alterations of amino acid metabolism in osteoarthritis: its implications for nutrition and health.

Li Y, Xiao W, Luo W, Zeng C, Deng Z, Ren W, Wu G, Lei G. Alterations of amino acid metabolism in osteoarthritis: its implications for nutrition and health. Amino Acids. 2016 Apr;48(4):907-14. doi: 10.1007/s00726-015-2168-x. Epub 2016 Jan 14. Review. PubMed PMID: 26767374.

Osteoarthritis (OA) is a common form of arthritis in humans. It has long been regarded as a non-inflammatory disease, but a degree of inflammation is now recognized as being a vital inducer of subpopulation of OA. Besides inflammation, the establishment and development of OA are associated with alterations in metabolism and profiles of amino acids (AA), including glutamate- and arginine-family AA as well as their related metabolites (e.g., creatinine, hydroxyproline, γ-aminobutyrate, dimethylarginines and homoarginine). Functional AA (e.g., glutamine, arginine, glutamate, glycine, proline, and tryptophan) have various benefits (i.e., anti-inflammation and anti-oxidation) in treatment of inflammation-associated diseases, including OA. Thus, these AA have potential as immunomodulatory nutrients for patients with inflammation-induced OA.


MSM (Methyl Sulfonyl Methane) CLINICAL STUDIES
Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement

Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement

Butawan M, Benjamin RL, Bloomer RJ. Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement. Nutrients. 2017;9(3):290. doi:10.3390/nu9030290.

Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has been well-investigated in animal models, as well as in human clinical trials and experiments. A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity. Initial evidence is available regarding the dose of MSM needed to provide benefit, although additional work is underway to determine the precise dose and time course of treatment needed to provide optimal benefits. As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects. This review provides an overview of MSM, with details regarding its common uses and applications as a dietary supplement, as well as its safety for consumption.

Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial

Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial.

Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF. Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage. 2006 Mar;14(3):286-94. Epub 2005 Nov 23. PubMed PMID: 16309928.

Osteoarthritis (OA) is the most common form of arthritis and the second most common cause of long-term disability among middle-aged and older adults in the United States. Methylsulfonylmethane (MSM) is a popular dietary supplement used as a single agent and in combination with other nutrients, and purported to be beneficial for arthritis. However, there is paucity of evidence to support the use of MSM. MSM (3g twice a day) improved symptoms of pain and physical function during the short intervention without major adverse events. The benefits and safety of MSM in managing OA and long-term use cannot be confirmed from this pilot trial, but its potential clinical application is examined. Underlying mechanisms of action and need for further investigation of MSM are discussed.


Boswellia (Boswellia Serrata) gum resin Extract CLINICAL STUDIES
Boswellia Serrata, A Potential Antiinflammatory Agent: An Overview

Boswellia Serrata, A Potential Antiinflammatory Agent: An Overview

Siddiqui MZ. Boswellia Serrata, A Potential Antiinflammatory Agent: An Overview. Indian Journal of Pharmaceutical Sciences. 2011;73(3):255-261. doi:10.4103/0250-474X.93507.

The resin of Boswellia species has been used as incense in religious and cultural ceremonies and in medicines since time immemorial. Boswellia serrata (Salai/Salai guggul), is a moderate to large sized branching tree of family Burseraceae (Genus Boswellia), grows in dry mountainous regions of India, Northern Africa and Middle East. Oleo gum-resin is tapped from the incision made on the trunk of the tree and is then stored in specially made bamboo basket for removal of oil content and getting the resin solidified. After processing, the gum-resin is then graded according to its flavour, colour, shape and size. In India, the States of Andhra Pradesh, Gujarat, Madhya Pradesh, Jharkhand and Chhattisgarh are the main source of Boswellia serrata. Regionally, it is also known by different names. The oleo gum-resins contain 30-60% resin, 5-10% essential oils, which are soluble in the organic solvents, and the rest is made up of polysaccharides. Gum-resin extracts of Boswellia serrata have been traditionally used in folk medicine for centuries to treat various chronic inflammatory diseases. The resinous part of Boswellia serrata possesses monoterpenes, diterpenes, triterpenes, tetracyclic triterpenic acids and four major pentacyclic triterpenic acids i.e. β-boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid and acetyl-11-keto-β-boswellic acid, responsible for inhibition of pro-inflammatory enzymes. Out of these four boswellic acids, acetyl-11-keto-β-boswellic acid is the most potent inhibitor of 5-lipoxygenase, an enzyme responsible for inflammation.

Natural anti-inflammatory agents for pain relief

Natural anti-inflammatory agents for pain relief

Maroon JC, Bost JW, Maroon A. Natural anti-inflammatory agents for pain relief. Surgical Neurology International. 2010;1:80. doi:10.4103/2152-7806.73804.

The Boswellia species are trees located in India, Ethiopia, Somalia, and the Arabian Peninsula, and they produce a gum resin called olibanum, better known in the western world as frankincense. This resin possesses anti-inflammatory, anti-arthritic, and analgesic properties. Boswellia can inhibit the leukotriene biosynthesis in neutrophilic granulocytes by inhibiting 5-LOX, thus affecting various inflammatory diseases that are perpetuated by leukotrienes.[95] Clinically, the substance is used in the treatment of degenerative and inflammatory joint disorders. It reduces the total white blood cell count in joint fluid, and it also inhibits leukocyte elastase, which is released in rheumatoid arthritis. In one recent study, a statistically significant improvement in arthritis of the knee was shown after 8 weeks of treatment with 333 mg B. serrata extract taken three times a day. The treatment improved function, but radiographically there was no change in the affected joints.[62]

Systematic review of herbals as potential anti-inflammatory agents: Recent advances, current clinical status and future perspectives

Systematic review of herbals as potential anti-inflammatory agents: Recent advances, current clinical status and future perspectives

Beg S, Swain S, Hasan H, Barkat MA, Hussain MS. Systematic review of herbals as potential anti-inflammatory agents: Recent advances, current clinical status and future perspectives. Pharmacognosy Reviews. 2011;5(10):120-137. doi:10.4103/0973-7847.91102.

A combination of Boswellia and curcumin showed superior efficacy and tolerability compared with nonsteroidal diclofenac for treating active osteoarthritis. Boswellia typically is given as an extract standardized to contain 30-40% boswellic acids (300-500 mg two or three times/day). Boswellia has been well tolerated in most studies, although some people may experience stomach discomfort, including nausea, acid reflux, or diarrhea.


Devils Claw CLINICAL STUDIES
[Devil's claw extract as an example of the effectiveness of herbal analgesics].

Devil's claw extract as an example of the effectiveness of herbal analgesics.

Chrubasik S. [Devil's claw extract as an example of the effectiveness of herbal analgesics]. Orthopade. 2004 Jul;33(7):804-8. Review. German. PubMed PMID: 15150687.

Preparations from devil's claw differ in their content of active ingredients as assessed by the quantity of harpagoside present. The harpagoside content in the daily dose of Doloteffin (extraction solvent water) is double that of preparations extracted with 60% ethanol. Only preparations with proven effectiveness for painful lower back or arthrotic pain are an attractive alternative to synthetic analgesics, and are of substantial benefit in the treatment of chronic pain. From an evidence based view, extract with at least 50 mg harpagoside in the daily dose should be recommended for the treatment of pain. Treatment with devil's claw extract is associated with a lower risk of adverse events than treatment with synthetic analgesics, and may contribute in the majority of patients to the relief of pain.

Treatment of patients with arthrosis of hip or knee with an aqueous extract of devil's claw (Harpagophytum procumbens DC.)

Treatment of patients with arthrosis of hip or knee with an aqueous extract of devil's claw (Harpagophytum procumbens DC.).

Wegener T, Lüpke NP. Treatment of patients with arthrosis of hip or knee with an aqueous extract of devil's claw (Harpagophytum procumbens DC.). Phytother Res. 2003 Dec;17(10):1165-72. PubMed PMID: 14669250.

Preparations made from the secondary tubers of Devil's claw (Harpagophytum procumbens) are successfully used in patients with rheumatic diseases (arthrosis and low back pain). In order to add data on the efficacy and long-term safety of an aqueous extract (Doloteffin; 2400 mg extract daily, corresponding to 50 mg harpagoside), which has been tested successfully in patients with low back pain, an uncontrolled multicentre drug surveillance study for about 12 weeks was conducted in 75 patients with arthrosis of the hip or knee. To standardize the assessment of treatment effects, the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index (10 point scale) as well as the 10 cm VAS pain scale were used. The results of the study revealed a strong reduction of pain and the symptoms of osteoarthritis. There was a relevant improvement of each WOMAC subscale as well as of the total WOMAC index: 23.8% for the pain subscale, 22.2% for the stiffness subscale and 23.1% for the physical function subscale. The WOMAC total score was reduced by 22.9%. VAS pain scores were decreased by 25.8% for actual pain, 25.2% for average pain, 22.6% for worst pain and 24.5% for the total pain score. The physicians reported a continuous improvement in typical clinical findings such as 45.5% for pain on palpation, 35% for limitation of mobility and 25.4% for joint crepitus. Only two cases of possible adverse drug reactions were reported (dyspeptic complaints and a sensation of fullness). Although this was an open clinical study, the results suggest that this Devil's claw extract has a clinically beneficial effect in the treatment of arthrosis of the hip or knee.

Herbal medicine for low‐back pain

Herbal medicine for low‐back pain

Oltean H, Robbins C, van Tulder MW, Berman BM, Bombardier C, Gagnier JJ. Herbal medicine for low-back pain. Cochrane Database of Systematic Reviews 2014, Issue 12. Art. No.: CD004504. DOI: 10.1002/14651858.CD004504.pub4.

Devil's claw, in a standardized daily dose of 50 mg or 100 mg harpagoside, may reduce pain more than placebo; a standardized daily dose of 60 mg reduced pain about the same as a daily dose of 12.5 mg of Vioxx®. While willow bark, in a standardized daily dose of 120 mg and 240 mg of salicin reduced pain more than placebo; a standardized daily dose of 240 mg reduced pain about the same as a daily dose of 12.5 mg of Vioxx® (a non‐steroidal, anti‐inflammatory drug). Cayenne was tested in several forms: in plaster form, it reduced pain more than placebo and about the same as the homeopathic gel Spiroflor SLR. Two other ointment‐based medications, S. officinale and S. chilensis appeared to reduce perception of pain more than placebo creams. Lavender essential oil applied by acupressure appeared effective in reducing pain and improving flexibility compared to conventional treatment. Adverse effects were reported, but appeared to be primarily confined to mild, transient gastrointestinal complaints or skinirritations.

Harpgophytum procumbens for osteoarthritis and low back pain: A systematic review

Harpgophytum procumbens for osteoarthritis and low back pain: A systematic review

Gagnier JJ, Chrubasik S, Manheimer E. Harpgophytum procumbens for osteoarthritis and low back pain: A systematic review. BMC Complementary and Alternative Medicine. 2004;4:13. doi:10.1186/1472-6882-4-13.

There is limited evidence for an ethanolic Harpagophytum extract containing less than <30 mg harpagoside per day in the treatment of knee and hip osteoarthritis. There is moderate evidence of effectiveness for (1) the use of a Harpagophytum powder at 60 mg harpagoside in the treatment of osteoarthritis of the spine, hip and knee; (2) the use of an aqueous Harpagophytum extract at a daily dose of 100 mg harpagoside in the treatment of acute exacerbations of chronic non-specific low back pain; and (3) the use of an aqueous extract of Harpagophytum procumbens at 60 mg harpagoside being non-inferior to 12.5 mg rofecoxib per day for chronic non-specific low-back pain (NSLBP) in the short term. Strong evidence exists for the use of an aqueous Harpagophytum extract at a daily dose equivalent of 50 mg harpagoside in the treatment of acute exacerbations of chronic NSLBP.

it may be concluded that treatment with Harpagophytum extract LI 174 may be expected to have a significant influence on sensory and vascular muscular response and bring about a reduction in muscle stiffness.

Effects of Harpagophytum procumbens LI 174 (devil's claw) on sensory, motor und vascular muscle reagibility in the treatment of unspecific back pain

Göbel, H., Heinze, A., Ingwersen, M. et al. Schmerz (2001) 15: 10. https://doi.org/10.1007/s004820170043

PROBLEM: This randomised, double-blind, placebo controlled study was intended to investigate the effects of Harpagophytum procumbens (Devil's Claw) on sensory, motor and vascular mechanisms of muscle pain. In addition to clinical efficacy and tolerability, possible action mechanisms were analysed by means of experimental algesimetric methods. METHODOLOGY: The study was performed on patients with slight to moderate muscular tension or slight muscular pain of the back, shoulder and neck. On a double-blind randomised basis the verum group received 2x1 film tablets per day, i. e. 2x480 mg/day, of Harpagophytum extract LI 174 (Rivoltan(R)) at 8.00 a.m. and 8.00 p.m. over a certain period. The duration of the therapy was 4 weeks. Data recording at 14-day intervals was made using a visual analogue scale, pressure algometer test, recording of antinociceptive muscular reflexes, muscle stiffness test, EMG surface activity, muscular ischaemia test, clinical global score and subjective patient and physician ratings. RESULTS: A total of 31 patients in the verum group and 32 in the placebo group were treated. After four weeks of treatment there was found to be a clear clinical efficacy of the verum on the clinical global score and in the patient and physician ratings. Highly significant effects were found in the visual analogue scale, the pressure algometer test, the muscle stiffness test and the muscular ischaemia test. No difference from placebo was found in the recording of antinociceptive muscular reflexes or in the EMG surface activity. Tolerability was good; no serious adverse effects occurred. CONCLUSIONS: A highly significant clinical efficacy was achieved with a monotherapy of Harpagophytum dry extract LI 174 after four weeks' treatment at a dosage of 2x480 mg/day in cases of slight to moderate muscular pain. With regard to the action mechanisms investigated, it may be concluded that treatment with Harpagophytum extract LI 174 may be expected to have a significant influence on sensory and vascular muscular response and bring about a reduction in muscle stiffness. No central nervous effects were discovered.

Current nutraceuticals in the management of osteoarthritis: a review

Current nutraceuticals in the management of osteoarthritis: a review

Akhtar N, Haqqi TM. Current nutraceuticals in the management of osteoarthritis: a review. Therapeutic Advances in Musculoskeletal Disease. 2012;4(3):181-207. doi:10.1177/1759720X11436238.

Osteoarthritis (OA) is a progressive degenerative joint disease that has a major impact on joint function and quality of life. Nutraceuticals and dietary supplements derived from herbs have long been used in traditional medicine and there is considerable evidence that nutraceuticals may play an important role in inflammation and joint destruction in OA. We review the biological effects of some medicinal fruits and herbs – pomegranate, green tea, cat’s claw, devil’s claw, ginger, Indian olibaum, turmeric and ananas – in an attempt to understand the pivotal molecular targets involved in inflammation and the joint destruction process and to summarize their toxicities and efficacy for OA management. So far there is insufficient reliable evidence on the effectiveness of ginger, turmeric and ananas. Pomegranate and green tea only have preclinical evidence of efficacy due to the lack of clinical data. In vivo and clinical studies are required to understand their targets and efficacy in OA. Limited in vitro and in vivo evidence is available for cat’s claw and Indian olibaum. More extensive studies are required before long-term controlled trials of whole cat’s claw and Indian olibaum extracts, or isolated active compounds, are carried out in patients with OA to determine their long-term efficacy and safety. Devil’s claw has not been rigorously tested to determine its antiarthritic potential in in vitro and in vivo models. There is strong clinical evidence of the effectiveness of devil’s claw in pain reduction. However, high-quality clinical trials are needed to determine its effectiveness. No serious side effects have been reported for any fruits and herbs. Overall, these studies identify and support the use of nutraceuticals to provide symptomatic relief to patients with OA and to be used as adjunct therapy for OA management. More high-quality trials are needed to provide definitive answers to questions related to their efficacy and safety for OA prevention and/or treatment.


Andrographis Paniculata CLINICAL STUDIES
Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial.

Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial

Burgos RA, Hancke JL, Bertoglio JC, Aguirre V, Arriagada S, Calvo M, Cáceres DD. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. Clin Rheumatol. 2009 Aug;28(8):931-46. doi: 10.1007/s10067-009-1180-5. Epub 2009 Apr 29. PubMed PMID: 19408036.

Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) possesses anti-inflammatory effects, attributed to the main constituent andrographolide proposed as alternative in the treatment of autoimmune disease. A prospective, randomized, double blind, and placebo-controlled study in patients with rheumatoid arthritis (RA) was performed. Tablets (Paractin) made of an extract of A. paniculata (30% total andrographolides) were administered three times a day for 14 weeks, after a 2-week washout period to 60 patients with active RA. The primary outcomes were pain intensity measured using a horizontal visual analog pain scale (VAPS). In addition, ACR, EULAR, and SF36 clinical parameters were recorded. The intensity of joint pain decreased in the active vs placebo group at the end of treatment, although these differences were not statistically significant. A significant diminishing for week in tender joint -0.13 95% confidence interval (CI; -0.22 to 0.06; p = 0.001), number of swollen joints -0.15 95%CI (-0.29 to -0.02; p = 0.02), total grade of swollen joint -0.27 95%CI (-0.48 to -0.07; p = 0.010), number of tender joints -0.25 95%CI (-0.48 to -0.02; p = 0.033), total grade of swollen joints -0.27 95%CI (-0.48 to -0.07; p = 0.01), total grade of tender joints -0.47 95%CI (-0.77 to -0.17; p = 0.002) and HAQ -0.52 95%CI (-0.82 to -0.21; p < 0.001) and SF36 0.02 95%CI (0.01 to 0.02; p < 0.001) health questionnaires was observed within the group with the active drug. Moreover, it was associated to a reduction of rheumatoid factor, IgA, and C4. These findings suggest that A. paniculata could be a useful "natural complement" in the treatment of AR; however, a larger trial and a more extended period of treatment is necessary in order to corroborate these results.

In vitro anti-inflammatory, analgesic and acute toxicity studies of ethanol extracts of Andrographis paniculata Nees and Spilanthus acemella Murr.

In vitro anti-inflammatory, analgesic and acute toxicity studies of ethanol extracts of Andrographis paniculata Nees and Spilanthus acemella Murr.

Singh Tanwer, B., Choudhary, S., & Vijayvergia, R. (2012). In vitro anti-inflammatory, analgesic and acute toxicity studies of ethanol extracts of Andrographis paniculata Nees and Spilanthus acemella Murr. . Pelagia Research Library.

The present study was carried out to evaluate the anti-inflammatory, analgesic and acute toxicity effects of Andrographis paniculata Nees and Spilanthus acemella Murr crude ethanolic extracts. The antiinflammatory activity was measured by carrageenan induced rat paw edema and analgesic activity was measured by acetic acid writhing test methods. 300mg/kg of S. acemella extract shown significant (p<0.05) antiinflammatory while 300mg/kg A. paniculata extract shown significant (p<0.05) analgesic activity as compared to diclofenac sodium. The ethanolic extracted has shown no toxic effect up to 1500 mg/kg body weight of Wister male rats. The results were obtained in a dose dependent manner. It may be concluded that the ethanolic extract of Andrographis paniculata Nees and Spilanthus acemella Murr has antiinflammatory and analgesic potential and have no toxic effect may be used as a future herbal medicine.

Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology

Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology

Okhuarobo A, Falodun JE, Erharuyi O, Imieje V, Falodun A, Langer P. Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology. Asian Pacific Journal of Tropical Disease. 2014;4(3):213-222. doi:10.1016/S2222-1808(14)60509-0.

Andrographis paniculata Wall (family Acanthaceae) is one of the most popular medicinal plants used traditionally for the treatment of array of diseases such as cancer, diabetes, high blood pressure, ulcer, leprosy, bronchitis, skin diseases, flatulence, colic, influenza, dysentery, dyspepsia and malaria for centuries in Asia, America and Africa continents. It possesses several photochemical constituents with unique and interesting biological properties. This review describes the past and present state of research on Andrographis paniculata with respect to the medicinal usage, phytochemistry, pharmacological activities, toxicity profile and therapeutic usage, in order to bridge the gap requiring future research opportunities. This review is based on literature study on scientific journals and books from library and electronic sources. Diterpenes, flavonoids, xanthones, noriridoides and other miscellaneous compounds have been isolated from the plant. Extract and pure compounds of the plant have been reported for their anti-microbial, cytotoxicity, anti-protozoan, anti-inflammatory, anti-oxidant, immunostimulant, anti-diabetic, anti-infective, anti-angiogenic, hepato-renal protective, sex hormone/sexual function modulation, liver enzymes modulation insecticidal and toxicity activities. The results of numerous toxicity evaluations of extracts and metabolites isolated from this plant did not show any significant acute toxicity in experimental animals. Detailed and more comprehensive toxicity profile on mammalian tissues and organs is needed in future studies.

Analgesic and Anti-inflammatory activity of Andrographis paniculata and Andrographolide in Diabetic Rodents

Analgesic and Anti-inflammatory activity of Andrographis paniculata and Andrographolide in Diabetic Rodents

Ajit Kumar Thakur., et al. “Analgesic and Anti-inflammatory activity of Andrographis paniculataand Andrographolide in Diabetic Rodents”. EC Pharmaceutical Science 1.1 (2015): 19-28.

An analytically characterized extract of Andrographis paniculata leaves (AP) and isolated pure andrographolide were evaluated for their analgesic and anti-inflammatory activity in diabetic rodents. AP (100, 200 and 400 mg/kg/day, p.o.), or andrographolide (30, 60 and 120 mg/kg/day, p.o.) was administered for ten consecutive days. Pentazocine and indomethacin were used as standard analgesic and anti-inflammatory drugs, respectively. Diabetic control animals were demonstrated significant abnormal pain-associated behaviours, measured as hyperalgesia to painful stimuli in tail flick test, hot plate test and formalin-evoked pain test, and exaggerated inflammatory responses in carragennan-induced paw oedema and cotton pellet induced granuloma tests in comparison to nondiabetic control animals. AP and andrographolide treatments in diabetic animals demonstrated significant analgesic and anti-inflammatory activity in all these tests, and their maximal efficacies were always comparable to the standard drugs used. Taken together, these observations confirm that andrographolide is the major active constituent ofAndrographis paniculata, and strongly suggest that anti-inflammatory and analgesic efficacies of AP are entirely due to the presence of high contents of andrographolide present in it.


Quercetin CLINICAL STUDIES
Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials

Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials

Gupta SC, Patchva S, Aggarwal BB. Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials. The AAPS Journal. 2013;15(1):195-218. doi:10.1208/s12248-012-9432-8.

Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.

Quercetin: A Potential Natural Drug for Adjuvant Treatment of Rheumatoid Arthritis

Quercetin: A Potential Natural Drug for Adjuvant Treatment of Rheumatoid Arthritis

Ji J-J, Lin Y, Huang S-S, Zhang H-L, Diao Y-P, Li K. Quercetin: A Potential Natural Drug for Adjuvant Treatment of Rheumatoid Arthritis. African Journal of Traditional, Complementary, and Alternative Medicines. 2013;10(3):418-421.

Rheumatoid arthritis (RA) is the rheumatism mainly manifested as disabling joint disease and mainly involves hands, wrists, feet and other small joints. Recurrent arthritis attacks, synovial cell hypertrophy and hyperplasia and bone and cartilage damages eventually lead to joint dysfunction and other complications, and there is no cure. Quercetin (QU) is a kind of natural flavonoids, with lipid-lowering, anti-inflammatory and other pharmacological activities, and minor toxic side effects. Thus, we assume that QU may be an adjuvant natural drug for treatment of RA. The possible mechanism is through regulation of NF-κB, to inhibit the transcription of joint synovitis factors, hinder the generation of inflammatory factors, and inhibit the inflammatory reaction; through inhibiting the activities of VEGF, bFGF, MMP-2 and other cytokines, to inhibit angiogenesis in multiple links and inhibit synovial pannus formation. QU may be an adjuvant natural drug for treatment of RA.


Curcumin CLINICAL STUDIES
The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis

The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis

Chin K-Y. The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis. Drug Design, Development and Therapy. 2016;10:3029-3042. doi:10.2147/DDDT.S117432.

Osteoarthritis is a degenerative disease of the joint affecting aging populations worldwide. It has an underlying inflammatory cause, which contributes to the loss of chondrocytes, leading to diminished cartilage layer at the affected joints. Compounds with anti-inflammatory properties are potential treatment agents for osteoarthritis. Curcumin derived from Curcuma species is an anti-inflammatory compound as such. This review aims to summarize the antiosteoarthritic effects of curcumin derived from clinical and preclinical studies. Many clinical trials have been conducted to determine the effectiveness of curcumin in osteoarthritic patients. Extracts of Curcuma species, curcuminoids and enhanced curcumin, were used in these studies. Patients with osteoarthritis showed improvement in pain, physical function, and quality of life after taking curcumin. They also reported reduced concomitant usage of analgesics and side effects during treatment. In vitro studies demonstrated that curcumin could prevent the apoptosis of chondrocytes, suppress the release of proteoglycans and metal metalloproteases and expression of cyclooxygenase, prostaglandin E-2, and inflammatory cytokines in chondrocytes. These were achieved by blocking the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) system in the chondrocytes, by preventing the activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, phosphorylation, and translocation of the p65 subunit of NF-κB complexes into the nucleus. In conclusion, curcumin is a potential candidate for the treatment of osteoarthritis. More well-planned randomized control trials and enhanced curcumin formulation are required to justify the use of curcumin in treating osteoarthritis.

Antinociceptive effects of curcumin in a rat model of postoperative pain

Antinociceptive effects of curcumin in a rat model of postoperative pain

Zhu Q, Sun Y, Yun X, Ou Y, Zhang W, Li J-X. Antinociceptive effects of curcumin in a rat model of postoperative pain. Scientific Reports. 2014;4:4932. doi:10.1038/srep04932.

Curcumin is a principal ingredient of traditional Chinese medicine, Curcuma Longa, which possesses a variety of pharmacological activities including pain relief. Preclinical studies have demonstrated that curcumin has antinociceptive effects for inflammatory and neuropathic pain. This study examined the effects of curcumin in a rat model of postoperative pain. A surgical incision on the right hind paw induced a sustained mechanical hyperalgesia that lasted for 5 days. Acute curcumin treatment (10–40 mg/kg, p.o) significantly and dose dependently reversed mechanical hyperalgesia. In addition, repeated curcumin treatment significantly facilitated the recovery from surgery. In contrast, repeated treatment with curcumin before surgery did not impact the postoperative pain threshold and recovery rate. All the doses of curcumin did not significantly alter the spontaneous locomotor activity. Combined, these results suggested that curcumin could alleviate postoperative pain and promote recovery from the surgery, although there was no significant preventive value. This study extends previous findings and supports the application of curcumin alone or as an adjunct therapy for the management of peri-operative pain.


White Willow Bark CLINICAL STUDIES
Medicinal potential of willow: A chemical perspective of aspirin discovery

Medicinal potential of willow: A chemical perspective of aspirin discovery

Mahdi JG. Medicinal potential of willow: A chemical perspective of aspirin discovery. Saudi Chem. Soc., 14, 317 – 322 (2010).

The willow tree is a symbolic medicinal plant that has been associated with the discovery of aspirin, chemically known as acetylsalicylic acid, or salicylate, which still offers surprises as a revival drug. The philosophical perspective of the significance of the willow tree has been elaborated since the Assyrians (4000 BC) and Sumerians (3500 BC), who were aware of its medicinal merits. In 1838, the main pharmacologically active ingredient of willow, the salicin structure was elucidated by hydrolysis to comprise D-glucose and salicyl alcohol. These uncovered new perspectives, which eventually lead to the discovery of aspirin.

Herbal medicine for low-back pain

Herbal medicine for low-back pain

Oltean H, et al. Herbal medicine for low-back pain. Cochrane Database Syst Rev. 2014 Dec 23;(12):CD004504. doi: 10.1002/14651858.CD004504.pub4. Review. PubMed PMID: 25536022.

BACKGROUND:
Low-back pain (LBP) is a common condition and imposes a substantial economic burden upon people living in industrialized societies. A large proportion of people with chronic LBP use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal medicines have been purported for use in treating people with LBP. This is an update of a Cochrane Review first published in 2006.
OBJECTIVES:
To determine the effectiveness of herbal medicine for non-specific LBP.
SEARCH METHODS:
We searched the following electronic databases up to September 2014: MEDLINE, EMBASE, CENTRAL, CINAHL, Clinical Trials.gov, World Health Organization International Clinical Trials Registry Portal and PubMed; checked reference lists in review articles, guidelines and retrieved trials; and personally contacted individuals with expertise in this area.
SELECTION CRITERIA:
We included randomized controlled trials (RCTs) examining adults (over 18 years of age) suffering from acute, sub-acute, or chronic non-specific LBP. The interventions were herbal medicines which we defined as plants used for medicinal purposes in any form. Primary outcome measures were pain and function.
DATA COLLECTION AND ANALYSIS:
A library scientist with the Cochrane Back Review Group conducted the database searches. One review author contacted content experts and acquired relevant citations. We downloaded full references and abstracts of the identified studies and retrieved a hard copy of each study for final inclusion decisions. Two review authors assessed risk of bias, GRADE criteria (GRADE 2004), and CONSORT compliance and a random subset were compared to assessments by a third individual. Two review authors assessed clinical relevance and resolved any disagreements by consensus.
MAIN RESULTS:
We included 14 RCTs (2050 participants) in this review. One trial on Solidago chilensis M. (Brazilian arnica) (20 participants) found very low quality evidence of reduction in perception of pain and improved flexibility with application of Brazilian arnica-containing gel twice daily as compared to placebo gel. Capsicum frutescens cream or plaster probably produces more favourable results than placebo in people with chronic LBP (three trials, 755 participants, moderate quality evidence). Based on current evidence, it is not clear whether topical capsicum cream is more beneficial for treating people with acute LBP compared to placebo (one trial, 40 participants, low quality evidence). Another trial found equivalence of C. frutescens cream to a homeopathic ointment (one trial, 161 participants, very low quality evidence). Daily doses of Harpagophytum procumbens (devil's claw), standardized to 50 mg or 100 mg harpagoside, may be better than placebo for short-term improvements in pain and may reduce use of rescue medication (two trials, 315 participants, low quality evidence). Another H. procumbens trial demonstrated relative equivalence to 12.5 mg per day of rofecoxib (Vioxx®) but was of very low quality (one trial, 88 participants, very low quality). Daily doses of Salix alba (white willow bark), standardized to 120 mg or 240 mg salicin, are probably better than placebo for short-term improvements in pain and rescue medication (two trials, 261 participants, moderate quality evidence). An additional trial demonstrated relative equivalence to 12.5 mg per day of rofecoxib (one trial, 228 participants) but was graded as very low quality evidence. S. alba minimally affected platelet thrombosis versus a cardioprotective dose of acetylsalicylate (one trial, 51 participants). One trial (120 participants) examining Symphytum officinale L. (comfrey root extract) found low quality evidence that a Kytta-Salbe comfrey extract ointment is better than placebo ointment for short-term improvements in pain as assessed by VAS. Aromatic lavender essential oil applied by acupressure may reduce subjective pain intensity and improve lateral spine flexion and walking time compared to untreated participants (one trial, 61 participants,very low quality evidence). No significant adverse events were noted within the included trials.
AUTHORS' CONCLUSIONS:
C. frutescens (Cayenne) reduces pain more than placebo. Although H. procumbens, S. alba, S. officinale L., S. chilensis, and lavender essential oil also seem to reduce pain more than placebo, evidence for these substances was of moderate quality at best. Additional well-designed large trials are needed to test these herbal medicines against standard treatments. In general, the completeness of reporting in these trials was poor. Trialists should refer to the CONSORT statement extension for reporting trials of herbal medicine interventions.

Efficacy and Safety of White Willow Bark (Salix alba) Extracts

Efficacy and Safety of White Willow Bark (Salix alba) Extracts

Shara M, Stohs SJ. Efficacy and Safety of White Willow Bark (Salix alba) Extracts. Phytother Res. 2015 Aug;29(8):1112-6. doi: 10.1002/ptr.5377. Epub 2015 May 22. Review. PubMed PMID: 25997859.

Willow bark extract has been used for thousands of years as an anti-inflammatory, antipyretic, and analgesic. In spite of its long history of use, relatively few human and animal studies have been published that confirm anecdotal observations. A small number of clinical studies have been conducted that support the use of willow bark extracts in chronic lower back and joint pain and osteoarthritis. Willow bark extracts also are widely used in sports performance and weight loss products presumably because of anti-inflammatory and analgesic activities, although no human studies have been published that specifically and directly document beneficial effects. In recent years, various in vitro and animal studies have demonstrated that the anti-inflammatory activity of willow bark extract is associated with down regulation of the inflammatory mediators tumor necrosis factor-α and nuclear factor-kappa B. Although willow bark extracts are generally standardized to salicin, other ingredients in the extracts including other salicylates as well as polyphenols, and flavonoids may also play prominent roles in the therapeutic actions. Adverse effects appear to be minimal as compared to non-steroidal anti-inflammatory drugs including aspirin. The primary cause for concern may relate to allergic reactions in salicylate-sensitive individuals.