It is the accumulation of insults, often nutritional, that gradually lead the body into inflammation and, as a result, accelerated ageing. Making the right changes to your nutrition and lifestyle that are going to create for you a way of living, but also show you how to reverse the process more speedily with natural anti-inflammatories the majority of which appear to be without a downside in terms of adverse effects. That means you can start to reduce pain right now. Some of these natural anti-inflammatories are not causative in the sense that, for example, a lack of curcumin-containing turmeric is not the cause of arthritis even though it can help reduce the pain and damaging state of permanent inflammation. All I need do is tell you how they work and how much to take.
Others are causative such as a lack of vitamin D, omega-3 or insulin-resistance, itself the result of a lifetime of too much sugar and carbohydrates.
The best natural painkillers are:
- Curcumin in turmeric
- Quercetin, naturally high in red onions
- Olive compounds including oleocanthal and hydroxytyrosol
- Omega-3 fats
- High dose vitamin D, or getting your blood level optimal
- Reversing insulin resistance
- Increasing your antioxidant & polyphenol intake
- Finding and eliminating your food intolerances
- Lowering your homocysteine level
- Glucosamine and Chondroitin
- MSM, a highly absorbable form of sulphur
Those shown in bold are my favourites. Most of the others depend on transforming your diet. Vitamin D and omega-3 are also worth supplementing. Tackling these issues, and supplementing combinations of these remedies almost always result in success in my clinical experience.
The last three, while anti-inflammatory, are the most important for rebuilding cartilage, the material at the end of bones that breakdown thus help to rebuild joints once you’ve got inflammation under control.
Of all the anti-inflammatory agents curcumin, found in the bright yellow pigment in turmeric has the most positive evidence and almost deserves a chapter in its own right. It has been known about and used medicinally for thousands of years dating back to the early Ayurvedic medicine coming out of India. I recall, when travelling in the ‘80s through Africa, an old man with a yellow stained bandage around his knee. This was a turmeric compress.
Astonishingly, an American company tried to get a patent on turmeric in 1995, claiming it was a ‘new’ discovery for the treatment of inflammation. But the Indian government successfully challenged this on the grounds that the spice had been used for precisely that purpose for generations in India. Turmeric gives a great flavour in curries, stir-fries or add a teaspoon when cooking rice. The only downside is that it can stain, so take care when using in cooking!
What has really brought curcumin-rich supplements into the spotlight is the discovery of ways to enhance its absorption into the bloodstream. Typically, when ground turmeric is eaten there is very little increase in available curcumin in the bloodstream however a new generation of supplements has increased absorption at least a hundred fold. Consequently, early studies often involved injecting it directly into the bloodstream and showing powerful effects that could not then be achieved just by having a teaspoon of turmeric powder.
Plenty of studies show it works as well as anti-inflammatory drugs, but without the side effects1. Like NSAIDs, it blocks the formation of the pro-inflammatory prostaglandins (PGE2), as well as leukotrienes. 2 In fact, it turns out to be what everyone hoped drugs like Vioxx would be (a mild 5-Lox and Cox-2 inhibitor that not does not affect Cox-1).There is no evidence of any downsides, even in high doses of 8g a day. It also mops up nitric oxide (another inflammatory mediator) and is a powerful antioxidant. In addition, it has been shown to promote detoxification. A review of Turmeric in the Journal of Clinical Immunology states that curcumin at low doses can also enhance antibody responses.3This suggests that curcumin's reported beneficial effects in arthritis, allergies, asthma, atherosclerosis, heart disease, Alzheimer's, and cancer might be due in part to its ability to modulate the immune system and dampen down inflammation.
Let’s take a look at the actual results of clinical studies in people suffering from either osteo or rheumatoid arthritis. Many studies focus on knee osteoarthritis since it is easier to quantify beneficial effects. I’ll focus on ‘double blind’ placebo-controlled studies whereby the sufferer doesn’t known whether they’ve been given a dummy pill or the curcumin rich supplements, and nor does the researcher, until the trial is over so they cannot ‘cheat’ in their clinical assessment of improvement. Some trials, instead of comparing the placebo, compare to the best currently offered NSAID drug treatment to see if curcumin is as good as, better or worse compared to NSAIDs.
Curcumin helps osteoarthritis just as well as NSAIDs. Here’s what studies show:
- A study in 2019 from the University of Liege in Belgium evaluated the effect of a high and lower dose of a turmeric extract high in curcumin (equivalent to 187 and 280 mg of curcumin ) in 150 patients with knee arthritis.4 After 3 months pain was reduced by 47 per cent in the high and 58 per cent in the low turmeric extract dose groups, which was statistically significantly better than placebo. They also needed to use less pain killers. In most measures the low dose was just as effective as the high dose of this ‘bio-optimised’ form of curcumin which was measured to raise blood levels of curcumin showing it was effectively absorbed.
- A short trial of another highly absorbable form of curcumin called Theracurmin® tested the effects of giving a 700mg capsule three times a day to people with osteoarthritis of the knee either doing or not doing a 30 minute session of aerobic and weight training. After four weeks both groups reported less pain and enhanced muscular and balancing function.5 The greatest benefit, however, was in the group taking Theracurmin and not doing the knee exercises. They had better knee flexion, substantially less pain and better physical function and ability to climb stairs after a month on the Theracurmin. (This is not to say that these exercises were not good but just that this added activity slightly masked the potential benefit of Theracurmin. Those exercising did have improved physical function and knee flexion.
- An earlier study in 2014 from Japan6 using another highly absorbable form of curcumin called Theracurmin (180mg) in 41 people with knee arthritis reported a significant 62 per cent improvement in pain (versus 50 per cent in the placebo group) and consequently those taking Theracurmin ended up reducing their use of other painkilling medication.
- Another similar study from India7comparing 160mg of curcumin versus 400mg ibuprofen in 50 people with knee arthritis found that pain scores more than halved in both groups over the 90 days with no significant difference between groups. In other words curcumin was just as effective as this NSAID drug.
- Another study conducted in Thailand compared a high dose of curcumin (1500mg) with a with ibuprofen (1,200mg) per day for four weeks in 331 knee arthritis sufferers.8 Improvements in pain stiffness and overall functions were similar in both groups but there less gastrointestinal adverse effects in the curcumin group than the drug group which is one of the problems with continuous NSAID use.
- Another study from India9, this time comparing a higher dose of curcumin (500mg) given three times daily with the NSAID diclonofenac found that pain reduced from 7.8 to 2.2 (out of a maximum score of 10) after 4 weeks in both groups. Function and quality of life also improved to similar extents in both groups. Once again, curcumin was just as effective as this painkiller. This confirmed an earlier pilot study11 involving 19 patients five of which were able to stop their pain medication completely while eleven were able to reduce it. None in the placebo group were able to stop their medication.
- For practical reasons most studies are up to 3 months long but one Italian study looked at the effect of a bioavailable form of curcumin over 8 months, compared to those on the best available drug treatment in a hundred osteoarthritis sufferers.According to Hippocrates “Illnesses do not come upon us out of the blue. They are developed from small daily sins against Nature. When enough sins have accumulated illnesses will suddenly appear.” What a visionary he was because that’s exactly what today’s medical science is showing. Pain, stiffness, physical, social and emotional functions all improved by more than 50per cent in the curcumin group, with no significant improvements in the control group on medication. There were also a significant improvements in inflammatory markers including ESR and IL-6 and a 63per cent decrease in NSAID use in the curcumin group with very few and minor adverse effects.
There are other studies but suffice it to say that curcumin works for osteoarthritis. Even by 2016 a systematic review combining the results of eight studies concluded that turmeric extracts high in curcumin were significantly better than placebo and equal to common painkilling medication and therefore superior given their very low incidence of adverse effects.12
Curcumin works for rheumatoid arthritis
But what about rheumatoid arthritis? A ‘good standard’ double-blind placebo-controlled trial gave rheumatoid arthritis suffers either a placebo or a low dose (250mg) or high dose (500mg) of a curcumin preparation for 90 days13. Both the low and the high curcumin groups experienced a statistically and clinically significant improvements in disease activity (53per cent-66per cent improvement), symptoms (62per cent-72per cent), inflammatory markers measuring both ESR and CRP (30per cent-89per cent) and rheumatoid factor (80per cent-84per cent). There were no improvements in the placebo group. Although the high dose group had slightly better average improvements the difference was not great enough to be statistically significant but this was probably to do with the relatively small study size – 12 in each group. (It’s a bit like tossing coins: if you tossed 5 heads and 8 tails you good say it was just luck. But if you tossed 500 heads and 800 tails that would be significant.)
This confirmed an earlier study from Kerala in India in 2012, which compared improvement in rheumatoid arthritis suffers either on the painkiller diclofenac or curcumin or both and found that, not only did the curcumin only group show more improvements than the drug group they also had much less adverse effects.14
One four month study comparing the effects of curcumin with glucosamine with chondroitin found just they both worked in reducing pain, stiffness and overall function, but the curcumin was slightly better.15
I highly recommend curcumin extracts in both osteoarthritis and rheumatoid arthritis. The form that is the most effective, both in raising blood levels of curcumin and in clinical trials is Theracurmin.
There is more truth to the expression ‘an apple a day keeps the doctor away’ than you may think! Apples are a good source of quercitin, which is a naturally occurring bioflavonoid that is increasingly used in the treatment of inflammatory diseases (bioflavonoids are frequently found in nature alongside vitamin C). Many plant foods contain flavonoid compounds, which are known to inhibit inflammation.16 These are found in fruits and vegetables, especially in red/blue foods such as berries and beetroot, as well as red onions. One red onion, or a cup of berries, or three servings of greens provides about 10mg of quercitin. Other good sources of quercitin include red wine, tea, grapefruit, broccoli, squash, red grapes, cranberries and citrus fruits. This is one reason why vegetarian diets have proven highly effective in reducing pain and inflammation.
Quercitin is a potent anti-inflammatory and one of the most abundant antioxidants.17 It works with Vitamin C and E to protect against free-radical damage and also helps stabilise cells and reduce the breakdown of collagen (the material needed by the body to maintain healthy joint tissue) - all of which are important in the management of arthritis.
It inhibits the production of the pro-inflammatory Cox and Lox enzymes and other inflammatory cytokines18 as well as prostaglandins (type 2)19 and also inhibits the release of histamine, which is involved in inflammatory reactions. Quercitin helps zinc, another key antioxidant mineral, get inside cells20.
A study in 2017 from the University of Medical Sciences in Tehran, Iran,21evaluated the effect of 500mg of quercetin in 50 women with rheumatoid arthritis. After eight weeks, quercetin abolished early morning stiffness and reduced morning pain by 42 per cent and after-activity pain by 37 per cent, while pain increased in the placebo group. Disease activity, overall wellbeing and disability assessment also significantly improved in the quercetin group.
More studies, especially in osteoarthritis, are needed but I put this highly versatile ant-inflammatory in the first line of defence against any inflammatory disease, with an effective daily amount being 500mg, ideally taken as 250mg twice or three times a day. There would be no harm and probably more benefit, in doubling this dose in acute inflammation. Quercitin is available in health food stores as a stand alone supplement and is also in some combination formulas.
The Truth About Glucosamine
One of the best known non-drug treatments for joint pain is glucosamine, an essential part of the building material for joints and the cellular ‘glue’ that holds the entire body together. It is a naturally occurring amino sugar (a molecule combining an amino acid with a simple sugar) and found in almost all the tissues of your body, although joint cartilage contains a higher concentration of glucosamine than any other structural tissue. It is used to make N-acetylglucosamine which, in turn, is one of the building blocks for the making of cartilage.
Daily wear and tear on our joints means that the connective tissue that surrounds them (cartilage, tendons, and ligaments) requires constant renewal, needing an ongoing supply of glucosamine. Unfortunately, it appears that some people are less able to make glucosamine as they get older. When this rebuilding process slows down, the result is degenerative joint diseases such as arthritis.
The mechanism by which glucosamine appears to stop or reverse joint degeneration is by providing the body with the materials needed to build and repair cartilage. It plays a fundamental role in the formation of joints, tendons, ligaments, synovial fluid, bone and many more body parts, including skin and blood vessels. Cartilage in joints consists of cells embedded in collagen that sits within a framework of watery ‘proteoglycan’ gel – it is the integrity of this structure that allows joints to remain flexible and able to resist the pressure of impact and gravity. So glucosamine appears to stop or reverse joint degeneration by providing the body with the materials it needs to form these proteoglycans (the framework for joint structure) and may prevent their breakdown in the body.23There is also some evidence that glucosamine helps the incorporation of sulphur into cartilage – sulphur is an essential nutrient for keeping all connective tissue stable.24
Although the body can make glucosamine, if you’ve got damaged joints you are unlikely to make enough - unless you are in the habit of munching on sea shells, which is the richest dietary source. Taking a substantial quantity of glucosamine as a nutritional supplement has been shown to slow down or even reverse this degenerative process. There are about 440,000 joint replacements every year in the US, and many could be avoided with the right nutrition. But how does glucosamine do the job?
Glucosamine appears to be particularly effective in protecting and strengthening the cartilage around your knees, hips, spine and hands. And while it can do little to actually restore cartilage that has completely worn away, it helps to prevent further joint damage and appears to slow the development of mild to moderate osteoarthritis. As mentioned earlier, traditional NSAIDs prescribed for arthritis actually impair your body’s cartilage-building capacity.
A 2001 study in The Lancet reported that glucosamine actually slowed the progression of osteoarthritis of the knee.25 Over the course of three years, they measured spaces between the patients’ joints and tracked their symptoms. Those on glucosamine showed no further narrowing of joints in the knee, which is an indicator of thinning cartilage. Put another way, glucosamine appeared to protect the shock-absorbing cartilage that cushions the bones. In contrast, the condition of the patients taking the placebo steadily worsened.
Because glucosamine helps to reinforce the cartilage around your joints, it may hasten the healing of acute joint injuries such as sprained ankles or fingers, and of muscle injuries such as strains. In strengthening joints, glucosamine also helps to prevent future injury.
Back pain control
Glucosamine strengthens the tissues supporting the spinal discs that line the back. It may therefore improve back pain resulting from either muscle strain or arthritis, and speed the healing of strained back muscles. Glucosamine seems to have similar effects on pain in the upper spine and neck.
As your body ages, the cartilage supporting and cushioning all of your joints tends to wear down. By protecting and strengthening your cartilage, glucosamine may help to postpone this process and reduce the risk of osteoarthritis.
In addition, most studies indicate that arthritis sufferers can move more freely and report increased overall mobility after taking glucosamine. In addition, several studies have shown that glucosamine can be as effective as NSAIDS for easing arthritic pain and inflammation, and there are less of the stomach-irritating side effects associated with NSAIDs.
Overall, the evidence for glucosamine is good. So good, in fact, the pharmaceutical industry have attempted to get it reclassified as a medicine and not a food.
A study in China of people with osteoarthritis of the knee found that participants taking 1500mg of glucosamine sulphate daily had a similar reduction in symptoms to those taking the NSAID ibuprofen, 1200mg daily. However, the glucosamine group tolerated their medicine much better.26 Another study compared the effects of glucosamine with ibuprofen painkillers. While the participants on the ibuprofen initially had a more dramatic reduction in pain, it stabilised after four weeks, whereas those on the glucosamine reported less pain after four and also after eight weeks.27
And in four high-quality 2005 studies that gave glucosamine sulphate versus NSAIDs, the glucosamine worked better in two, and was equivalent to the NSAIDs in the other two,28 again without the side effects.
Another study from the University of Siena, Italy29 evaluated the effect of 1,500mg glucosamine on its own versus placebo for 12 weeks in 60 patients with knee arthritis. Pain at rest and on moving improved significantly more in the glucosamine group than the placebo group, by 40 per cent and 16 per cent, respectively. Improvements continued for eight weeks after supplementation was stopped, but returned to baseline after another four weeks. You have to keep taking it.
Not all placebo controlled trials, however, have proven effective. Two earlier trials found significant reductions, almost a halving in pain, in both the glucosamine and placebo groups. So it does suggest there’s quite a remarkable ‘placebo’ effect if you’re taking something you think works. That’s why I prefer studies that measure biological inflammatory markers and physical measures of joint function, for example knee flexibility.
Most of the research has been done using glucosamine sulphate, but glucosamine hydrochloride is also known to inhibit Cox-2, which means it has an anti-inflammatory effect.30 A study in 2018 from Brazil compared the effect of different types of glucosamine: 1,500mg glucosamine sulfate plus 1,200mg chondroitin versus 1,500mg glucosamine hydrochloride plus 1,200mg chondroitin. 100 patients with knee arthritis took either combination for 12 weeks. Pain intensity reduced by 36% in the glucosamine sulfate group and by 44% in the glucosamine hydrochloride group but this difference wasn’t statistically significant.31
My advice is to aim for 500 to 1,500mg a day (the usual dosage for glucosamine in trials on its own is 500mg, three times daily). Bear in mind that trials weight there design to maximise the effect while, if you are also changing your diet and introducing other joint friendly nutrients you might not need such a hefty dose.
Many people find that the longer they use it, the more beneficial it feels. It works especially well when combined with MSM.
MSM for sulphur - the bone builder
MSM, which stands for methylsulfonylmethane, is one of the most effective sources of the essential mineral sulphur. If you think of building cartilage as similar to building a house, glucosamine supplies the body’s two-by-fours. These are essential for the framework, but you also need nails – and that’s where sulphur comes in.
As well as glucosamine, sulphur is essential for pain relief from arthritis since it is involved in a multitude of key body functions including pain control, inflammation, detoxification and tissue building. Some people have reported tremendous relief from arthritis by supplementing 1 to 6g of MSM.32 One possible reason for this remarkable effectiveness is that sulphur deficiency is far more common than realised. A study in 1995, reported in the book ‘The Miracle of MSM’, found that sulphur concentration is lower in the cartilage of those with arthritis.33 Since sulphur is an essential ingredient in cartilage formation, as well as inflammatory response, this may explain why MSM can be helpful.
Pain can be due to pressure changes in cells, which in turn affect the nerves that sense pain. If cells inflate due to excess build-up of fluid or a drop in the pressure surrounding them, the nerves register the pain. Perhaps this is why people with arthritis can predict pressure changes in the weather because of the pain they experience as it is approaching. MSM may also help improve cell membrane fluidity, thereby improving the exchange of fluids in and out of cells, and reducing pressure build-up.
Four trials show that MSM works. The first study, at the UCLA School of Medicine, found that on 2,250mg of MSM a day, patients with arthritis had an 80% improvement in pain within six weeks, compared with a 20% improvement in those who had taken dummy pills/placebos.34
Another US study at the Southwest College of Naturopathic Medicine & Health Sciences in Tempe compared the effect of 6g (6,000mg) of MSM against placebo for 12 weeks in 50 patients with knee osteoarthritis.35 In the MSM group, pain and joint function improved by almost a third and significantly better than the placebo group.
An Israeli study in 2011compared 3.4g of MSM for 12 weeks with placebo in 49 patients with knee arthritis.36 Pain and joint function improved by a fifth, again better than placebo.
While the effects of MSM on its own may not be as effective as glucosamine on its own a combination of both glucosamine and MSM giving 500mg of each, three times a day, is particularly effective.37 An unpublished double-blind study from 2003 giving 750mg of each to half a group of arthritis patients and a placebo to the other showed an 80 per cent improvement after six weeks in the first group compared to a 20 per cent improvement in the placebo group.38
If you have arthritis or joint pain I recommend that you supplement 500 to 1,500mg of glucosamine sulphate (or glucosamine hydrochloride) a day, together with 600 to 1,200mg of MSM. The lower end of the range is enough if you’re looking to support joints and prevent their degeneration, while the higher end of the range is for those who have aching joints or a history of joint problems or arthritis, and are looking to maximise recovery. MSM is available both as a balm and in capsules. The therapeutic dose appears to be between 600mg and 3000mg. It is certainly well worth trying.
Foods particularly rich in sulphur include eggs, onions and garlic, but sulphur is also found in all protein foods.
My new book Say No to Arthritis is out on 8 October (Piatkus). HOLFORDirect have recently NEW Glucosamine with Theracurmin(R) ,MSM and Quercetin in the Body Range as well as stocking supplement ranges to support many aspects of health.
1. N Chainani-Wu, ‘Safety and Anti-Inflammatory Activity of Curcumin: A Component of Tumeric (Curcuma longa).’ Journal of Alternative and Complementary Medicine, (2003), 9(1):161-8.
2. B Joe and B Lokesh, ‘Effect of curcumin and capsaicin on arachidonic acid metabolism and lysosomal enzyme secretion by rat peritoneal macrophages.’ Lipids, (1997), 32(11):1173–80.
3. G Jagetia and B Aggarwal, ‘Spicing up of the immune system by curcumin.’ Journal of Clinical Immunology, (2007), 27(1):19-35.
4. Y Henrotin et al,’Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study.’ Arthritis Research & Therapy, (2019), 21(1):179. https://doi.org/10.1186/s13075-019-1960-5
5. Y Shin et al, ‘Short-term effects of Theracurmin dose and exercise type on pain, walking ability, and muscle function in patients with knee osteoarthritis.’ J Exerc Rehabil, (2017), 13(6):684-92. doi: 10.12965/jer.1735064.532. PMID: 29326901; PMCID: PMC5747204.
6. Y Nakagawa et al, ‘Short-term effects of highly-bioavailable curcumin for treating knee osteoarthritis: a randomized, double-blind, placebo-controlled prospective study.’ Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association, (2014), 19(6):933–9. https://doi.org/10.1007/s00776-014-0633-0
7. P Gupte et al, ‘Evaluation of the efficacy and safety of Capsule Longvida((R)) Optimized Curcumin (solid lipid curcumin particles) in knee osteoarthritis: a pilot clinical study.’ Journal of Inflammation Research, (2019), 12:145-52. https://doi.org/10.2147/JIR.S205390
8. V Kuptniratsaikul et al, ‘Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study.’ Clinical Interventions in Aging, (2014), 9:451-8. https://doi.org/10.2147/CIA.S58535
9. D Shep et al, ‘Safety and efficacy of curcumin versus diclofenac in knee osteoarthritis: a randomized open-label parallel-arm study.’ Trials, (2019), 20(1):214. https://doi.org/10.1186/s13063-019-3327-2
10. Y Panahi et al, ‘Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial.’ Phytotherapy Research: PTR, (2014), 28(11):1625-31. https://doi.org/10.1002/ptr.5174
11. G Belcaro et al, ‘Efficacy and safety of Meriva(R), a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients.’ Alternative Medicine Review : A Journal of Clinical Therapeutic, (2010), 15(4):337-44.
12. J Daily e al, ‘Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.’ Journal of Medicinal Food, (2016), 19(8):717-29. https://doi.org/10.1089/jmf.2016.3705
13, A Amalraj et al, ‘A Novel Highly Bioavailable Curcumin Formulation Improves Symptoms and Diagnostic Indicators in Rheumatoid Arthritis Patients: A Randomized, Double-Blind, Placebo-Controlled, Two-Dose, Three-Arm, and Parallel-Group Study.’ Journal of Medicinal Food, (2017), 20(10):1022-30. https://doi.org/10.1089/jmf.2017.3930
14. B Chandranand A Goel, ‘A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis.’ Phytotherapy Research : PTR, (2012), 26(11):1719-25. https://doi.org/10.1002/ptr.4639
15. G Belcaro et al, ‘Meriva(R)+Glucosamine versus Condroitin+Glucosamine in patients with knee osteoarthritis: an observational study.’ European Review for Medical and Pharmacological Sciences, (2014), 18(24):3959-63.
16. M Lindahl and C Tagesson, ‘Flavonoids as phospholipase A2 inhibitors: importance of their structure for selective inhibition of group II phospholipase A2.’ Inflammation, (1997), 21(3):347–56.
17. Y Shaik et al, ‘Role of quercetin (a natural herbal compound) in allergy and inflammation.’ Journal of Biological Regulators and Homeostatic Agents, (2006), 20(3-4):47-52 .
18. Y Li et al, ‘Quercetin, Inflammation and Immunity.’ Nutrients. (2016), 8(3):167. doi:10.3390/nu8030167
19. A Negre-Salvayre et al, ‘Additional antilipoperoxidant activities of alpha-tocopherol and ascorbic acid on membrane-like systems are potentiated by rutin.’ Pharmacology, (1991), 42(5):262–72.
20. H Dabbagh-Bazarbachi et al, ‘Zinc ionophore activity of quercetin and epigallocatechin-gallate: from Hepa 1-6 cells to a liposome model.’ J Agric Food Chem. (2014), 62(32):8085-93. doi:10.1021/jf5014633
21. F Javadi et al, ‘The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women with Rheumatoid Arthritis: A Double-Blind, Randomized Controlled Trial.’ Journal of the American College of Nutrition, (2017) 36(1):9-15. [https://doi.org/10.1080/07315724.2016.1140093]
22. I Setnikar et al, ‘Pharmacokinetics of glucosamine in the dog and in man.’ Arzneimittel Forschung, (1986), 36(4):729-35.
23. K Karzel and K Lee, ‘Effect of hexosamine derivatives on mesenchymal metabolic processes of in vitro cultured fetal bone explants.’ Zeitschrift fur Rheumatologie, (1982), 41(5):212-8; I Setnikar et al, ‘Antireactive properties of glucosamine sulfate.’ Arzneimittel Forschung, (1991), 41(2):157-61.
24. M Muraty, ‘Glucosamine sulfate: effective osteoarthritis treatment.’ Amer J Nat Med, (1994), (10–14 Sept. 1994) – see https://altmedrev.com/wp-content/uploads/2019/02/v4-3-193.pdf
25. J Reginster et al, ‘Long-term effects of Glucosamine Sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial.’ The Lancet, (2001), 357(9252):251-6.
26. G Qui et al, ‘Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis.’ Arzneimittelforschung, (1998), 48(5):469-74.
27. V Lopes, ‘Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthrosis of the knee in out-patients.’ Current Medical Research and Opinion, (1982), 8(3):145-9.
28. T Towheed et al, ‘Glucosamine therapy for treating osteoarthritis.’ The Cochrane Database of Systematic Reviews, (2005), 2:CD002946
29. N Giordano et al, ‘The efficacy and tolerability of glucosamine sulfate in the treatment of knee osteoarthritis: A randomized, double-blind, placebo-controlled trial.’ Current Therapeutic Research, Clinical and Experimental, (2009), 70(3):185-196. [https://doi.org/10.1016/j.curtheres.2009.05.004]
30. B Jang et al, ‘Glucosamine hydrochloride specifically inhibits COX-2 by preventing COX-2 N-glycosylation and by increasing COX-2 protein turnover in a proteasome-dependent manner.’ Journal of Biological Chemistry, (2007), 282(38):27622-32.
31. A Lomonte et al, ‘Multicenter, randomized, double-blind clinical trial to evaluate efficacy and safety of combined glucosamine sulfate and chondroitin sulfate capsules for treating knee osteoarthritis.’ Advances in Rheumatology (London, England), (2018), 58(1):41. [https://doi.org/10.1186/s42358-018-0041-9]
32. Methylsulfonylmethane (MSM) Monograph, Alternative Medicine Review, (2003), 8(4):438-41
33. S Jacob et al, ‘The Miracle of MSM: The Natural Solution for Pain’, Putnam, 1999.
34. S Jacob and J Appleton, ‘MSM: The Definitive Guide. A Comprehensive Review of the Science and Therapeutics of Methylsulfonylmethane.’ (2003), Topanga, CA: Freedom Press, pp 107-121.
35. L Kim et al, ‘Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial.’ Osteoarthritis and Cartilage, (2006), 14(3):286-94. [https://doi.org/10.1016/j.joca.2005.10.003]
36. E Debbi et al, ‘Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study.’ BMC Complementary and Alternative Medicine, (2011), 11:50. [https://doi.org/10.1186/1472-6882-11-50]
37. P Usha and M Naidu, ‘Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis.’ Clinical Drug Investigation, (2004), 24(6):353-63.