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REPLAY: Four Perspectives: Chronic Pain and Inflammation Part 2

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REPLAY: Four Perspectives: Chronic Pain and Inflammation Part 2

In Part 2 of our Four Perspectives series on chronic pain and Inflammation, Professor Lesley Braun and the FX Medicine Ambassadors cover the economic burden that ongoing pain has on Australians and our economy. There are extensive treatment options available to holistic practitioners for resolving complex pain and inflammation.

Tune in as our experts detail therapeutic use of vitamin-C, curcumin, saffron, quercetin, PEA, specialised pro resolving mediators and fish oils, while exploring their mechanisms of action and therapeutic dosing. The discussion includes monitoring for safety, dietary and lifestyle factors and the collaborative approach to patient management. 

Covered in this episode

[00:30] Welcoming the Ambassadors and introducing today’s topic
[02:50] The importance of a holistic approach to resolving pain and inflammation
[03:41] The anti-inflammatory effects of the Mediterranean Diet
[05:58] Curcumin supplementation for pain
[08:48] Bioavailabilty of curcumin and therapeutic dosages 
[11:39] Saffron for depression and anxiety 
[16:10] Vitamin D supports muscle and nerves
[17:41] Quercetin and vitamin C for chronic and acute pain
[20:51] SPMs for resolution of inflammation
[25:31] PEA reduces pain hypersensitivity
[29:26] Omega-3s reduce pain and use of NSAIDs
[35:44] Boswellia improves pain and mobility in osteoarthritis
[38:05] NSAIDs can cause epigastric pain
[39:21] Utilising pain diaries for patients
[40:36] Lifestyle factors
[46:21] Collaboration and referrals
[49:10] Thanking the ambassadors and closing remarks

Key takeaways

  • One third of Australians live with chronic inflammation and cost the economy an estimated $73.2 billion in 2018. When untreated inflammation drives disease development 
  •  Treating the whole person is critical for resolving chronic pain and inflammation – consider food, stress, sleep quality and the microbiome. 
  • The Mediterranean Diet is well researched and shown to target underlying pathologies of disease and support the mood/somatic aspect of chronic pain. Central to the diet are cold water oily fish, nuts & seeds, vegetables, extra virgin olive oil, and garlic. 
  • Compounds in extra virgin olive oil have similar anti-inflammatory properties to Ibuprofen. 

Therapeutic considerations

  • Vitamin C
    • As little as 500mg of vitamin-C p/day can impact inflammatory biomarkers.
    • Can protect against environmental exposure of toxins. 
  • Curcumin 
    • Most useful in therapeutic doses of 500-1000mg p/day.
    • Only supplementation can provide these levels.  
    • MOA: antioxidant, anti-inflammatory, reduces cortisol, positive impact on neurotransmitters, liver and gut health 
  • Saffron
    • Dosing at 14 mg BD or 28 mg/day are useful for sleep issues 
    • MOA: impacts neurotransmitters, antioxidant, anti-inflammatory, novel research shows Heart Rate Variability is positively affected 
  • Vitamin D 
    • Supports musculoskeletal and nervous systems.  
    • MOA: modulates neuro-excitability of nerves, attenuates prostaglandin pathways and influences neuronal anti-inflammatory pathways 
  • Quercetin 
    • A flavonoid found in many fruits and vegetables. Therapeutic dosing of 500mg/d away from meals. 
    • MOA: anti-inflammatory, inhibits histamine release 
  • Specialised pro resolving mediators (SPMs)
    • Research shows those with chronic inflammation are not able to produce adequate amounts endogenously leading to a non-resolving inflammatory state.
    • 250mg/d for a month.
    • SPMs can be combined with curcumin for two months to improve pain, mood and quality of life. 
    • MOA: switches unresolved inflammation off and proceeds to the resolution phase 
  • Palmitoylethanolamide (PEA)
    • Another endogenous compound that’s compromised in those with chronic inflammation resulting in pain.
    • Dosing of 600mg BD 
    • MOA: inhibits mast cell degranulation, indirectly influences cannabinoid receptors through its “entourage” effect 
  • Omega-3’s EPA/DHA at a 2:1 ratio
    • Supportive for joint pain, longevity and reducing NSAID usage.
    • For maintenance of general health dosing of 1-2g p/day EPA and 500mg – 1g of DHA p/day.
    • For reducing pain and inflammation increase dose to 3-6g /day for min. 3 months. 
    • MOA: anti-inflammatory through influence on anti-inflammatory transcription factors,  
  • Boswelia
    • 200mg p/day for 8 weeks. 
    • MOA: anti-inflammatory, anti-arthritic, analgesic 
  • Pro-inflammatory foods commonly found in diets include alcohol, sugar and (for some people) dairy  
  • Lifestyle and psychosocial factors to consider: regular exercise, social isolation, feeling validated that an individual’s pain is real. 
  • Collaborating with your patient AND with other healthcare professionals including GPs, psychologists, chiropractors and physiotherapists, provides the best therapeutic outcomes.  

Resources discussed and further reading

Chronic pain

Research: Prevalence of chronic pain in LTCs and multimorbidity: A cross-sectional study using UK Biobank (Journal of Multimorbidity and Comorbidity, 2021)
Infographic: Chronic Pain and Central Sensitisation

Mediterranean diet and inflammation

Research: Molecular mechanisms of inflammation. Anti-inflammatory benefits of virgin olive oil and the phenolic compound oleocanthal (Curr Pharm Des, 2011)

 Vitamin C

Research: Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial (Drug Des Devel Ther., 2015)

 Omega-3 Fatty Acids

Research: Association of fish oil supplementation with risk of incident dementia: A prospective study of 215,083 older adults (Clin Nutr., 2022)
Research: Association of Oily and Nonoily Fish Consumption and Fish Oil Supplements With Incident Type 2 Diabetes: A Large Population-Based Prospective Study (Diabetes Care, 2021)
Research: Effect of ω-3 polyunsaturated fatty acids on arthritic pain: A systematic review (Nutrition, 2017)
Research: Omega-3 Polyunsaturated Fatty Acids and the Treatment of Rheumatoid Arthritis: A Meta-analysis (Archives of Medical Research, 2012)


Research: Management of osteoarthritis (OA) with the pharma-standard supplement FlexiQule (Boswellia): a 12-week registry (Minerva Gastroenterol Dietol., 2015)
Research: Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis (BMC Complement Med Ther., 2020)


Research: Effects of saffron on sleep quality in healthy adults with self-reported poor sleep: a randomized, double-blind, placebo-controlled trial (J Clin Sleep Med., 2020)
Research: An examination into the mental and physical effects of a saffron extract (affron®) in recreationally-active adults: A randomized, double-blind, placebo-controlled study (Journal of the International Society of Sports Nutrition, 2021)
Research: The Effects of a Saffron Extract (affron®) on Menopausal Symptoms in Women during Perimenopause: A Randomised, Double-Blind, Placebo-Controlled Study (J Menopausal Med. 2021)



Lesley: This is FX Medicine, bringing you the latest in evidence-based, integrative, functional, and complementary medicine. 

I begin today by acknowledging the traditional custodians of the land on which we gather and pay my respects to their elders, past and present. I extend that respect to Aboriginal and Torres Strait Islander peoples here today and wherever you are listening from. 

Hi, I am Professor Lesley Braun, director of Blackmores Institute and editor-in-chief of FX Medicine. Welcome to part two of our two-part series on chronic pain and inflammation.
We're back again talking with our four FX Medicine ambassadors; Dr. Adrian Lopresti, who's going to talk to us as a psychologist and also about the herbal medicine research that he's been doing in the space, Emma Sutherland, who brings us her naturopathic understanding, Lisa Costa-Bir, who adds her naturopathic view as well, and Dr. Michelle Woolhouse, our integrative GP. 

Hi, everybody, and welcome back.

Michelle: Hi, Lesley.

Emma: Hi Lesley.

Adrian: Hi Lesley.

Lisa: Hello.

Lesley: In part one of this series, we looked at the pain landscape, defining pain in its various forms. We looked at the biomedical and naturopathic approaches to pain and the psychological impacts of pain. We also discussed how to test and assess pain and inflammation, and also the importance of reframing as well as a lot of other things.

In part two, we are going to delve deeper into the natural medicines and those dietary and lifestyle approaches which are going to support the reduction and, ideally, the resolution of pain and inflammation. But I want to start with a few statistics. 

In fact, one in three Australians live with a chronic inflammatory condition. That means if you're sitting on a bus and you've got people on either side of you, one of those is going to be having chronic pain problems every single day. It's massive.

This has created, as you'd imagine, a huge financial burden to the community estimated at $73.2 billion in 2018 with projections to this number to more than double by 2050. If left untreated, inflammation plays a key role in disease development, and worryingly, the presence of chronic pain is also attributed to an increase in suicidal behaviour. So, these statistics have motivated all of us to look at this really seriously and try to better understand the role of diet, lifestyle, and also natural medicines as well.

Now, I'm going to start our conversation today by talking to Emma. As a naturopath, you've got years of experience taking a whole-person approach to the resolution of things like pain and inflammation. Why is that important, particularly in this situation?

Emma: Well, as naturopaths, we are trained to treat the whole person. It's one of our core philosophies, and we look through this lens of a holistic framework. It's how we both assess a case and then how we also put our protocols together. And I feel that whole-person approach is critical for the resolution of pain and inflammation. There are so many drivers involved in disease states, it's not just one single driver. Inflammation can be affected by the food we eat, the quality of our sleep, our stress levels, the state of our microbiome, and so many other factors. It's not a one-step wonder here.

Now, my bias is always towards a treatment protocol that involves diet and lifestyle strategies combined with therapeutic doses of herbal medicine and nutritional supplements, but I also come from a very strong food as medicine approach. Now, my favourite diet for inflammation is the traditional Mediterranean diet. It is the most researched diet globally and the benefits are very well documented.

Now, the overall basis is a shift of diet towards including more foods that have an anti-inflammatory effect. And a Mediterranean diet has been shown to confer protection against the pathology of chronic diseases, things like cardiovascular disease, cancer, and respiratory illness. The foods that we want to be recommending here include cold water oily fish, nuts, seeds, vegetables, extra virgin olive oil, and of course, garlic. Many of these foods are also high in antioxidants and polyphenols, which are naturally protective. And in fact, it was a 2011 study that showed compounds in extra virgin olive oil have similar anti-inflammatory properties to ibuprofen, so there really is something in this. 

But I want to just not overlook the basics either. So, something as simple as vitamin C, when we're treating pain and inflammation. A study involving patients with metabolic syndrome showed that as little as 500 milligrams of vitamin C twice a day reduced their inflammatory biomarkers, things like CRP and interleukin-6. So, food really can be medicine as far as I'm concerned.

Lesley: The thing that's really interesting about the Mediterranean diet, because it just keeps coming up. What can't that diet do, really? It's one of those diets that I think has been proven to reduce all-cause mortality, as you said, as well as improve mood and also mood disorders, which we know there's a link between mood and chronic pain, too. So, it would cover that, I'm guessing.

Emma: Yeah, I'd imagine it's working from so many different angles. As we've spoken about in part one, the mind-body aspect of pain and inflammation can really be attenuated by a Mediterranean diet, too.

Lesley: Which is also yummy.

Emma: It's delicious.

Lesley: Adrian, I know you've been doing so much research on herbal medicines in this space. Really, you are one of the absolute experts in this area. Curcumin's become so popular. You see it everywhere. I was in India a couple of months ago, and obviously, they've known about the secrets of curcumin for such a long time, but not all curcumins are the same, we know, and I think as the science is developing we're learning more about what it can do and can't do. Can you tell us a bit more about what you're seeing with curcumin?

Adrian: Yeah, definitely. Most people will know that curcumin is derived from turmeric but it's not the same as turmeric. So, turmeric, obviously, you eat and you can use it as part of your food and so forth, but curcumin only comprises of about 2% to 5% of turmeric. So, when we think about people having turmeric lattes and adding turmeric to their food and so forth, that's brilliant, and I encourage people to do that as an ongoing health and part of the diet that they should be eating. But when it comes to curcumin, you really need to supplement with curcumin because basically, if you want to derive the therapeutic amounts of curcumin that we've done in research trials, you're probably going to be taking — I can never predict it — but somewhere between 5 and 10 tablespoons of turmeric a day. So, you'll no longer have chronic pain or if have a different type of pain, it would be a gastrointestinal type pain.

Lesley: I'll hate to say it. No, I'm not going to say it.

Adrian: So, that's something to consider. So, curcumin, yes, it's from turmeric, but it's not the same as turmeric, although it's derived from turmeric. And the research shows that curcumin is an anti-inflammatory, it's a potent antioxidant. It seems to also have an effect on our HPA axis, which is our stress response, and so potentially has an impact on cortisol levels, which is our stress hormone. It affects our neurotransmitters, which are important for mood and sleep, and also important for pain, too. So, those neurotransmitters, many neurotransmitters are also associated with pain.

And even may affect the gut function. And there's also some research showing now that our microbiome, our gut bacteria can also potentially affect pain. So, you've got different mechanisms whereby curcumin could have a positive impact on pain and on mood.

And there's been trials on curcumin looking at osteoarthritis, and there's been some positive trials and its effect on osteoarthritis. There's some positive trials on rheumatoid arthritis. There's some research around migraine, not a lot. There's some research and there's one that I did with curcumin for IBS and gastrointestinal-type pain. So, there's been some research around curcumin having a positive effect on pain conditions. And also, I've done a lot of research on curcumin in terms of its impact on depression. So, potentially, taking curcumin could reduce pain, but also could potentially improve mood. So, I’d highly recommend curcumin as an option for people who are experiencing pain.

Lesley: So, you've got curcumin. It almost sounds like a polypill, but it's just one ingredient, isn't it? It's inflammation, it's pain, it's mood as well. But I have read that curcumin is not that well absorbed from food sources and sometimes you need curcumin that's got some enhancement to make it more bioavailable. Have you read much about that as well?

Adrian: Yeah, definitely. That's an issue with curcumin is its bioavailability. So, in terms of taking curcumin and then trying to detect how much of the curcumin is absorbed into the bloodstream, the research shows that it's poorly absorbed into the bloodstream. So, there are different options and different ways that people can increase the bioavailability of curcumin. And one of those is, traditionally, people have used black pepper extracts to help increase the bioavailability.

But nowadays, there's also different forms of curcumin that are more bioavailable. And I think that's probably better than just having the black pepper extract. The research actually shows it's more bioavailable from that perspective. But saying that, what we don't know is, yes, it gets more into the bloodstream, but does increased bioavailability result in increases in therapeutic effectiveness? I suspect it does, but we still don't know. So, certainly, I would recommend that people, if they're going to take curcumin, I would choose a more bioavailable form, one that's been researched to increase its impact on, obviously, its absorption into the blood. And there's different options available to people there.

And then in terms of its therapeutic dosages, the research shows generally between five (hundred milligrams) to one gram a day is where most studies have used in terms of curcumin, in terms of dosages, but there are studies where it's used up to six grams a day. So, I wouldn't necessarily recommend that, certainly not for chronic use, but if somebody is experiencing acute pain, maybe having a higher dose would be something I would recommend initially, and then after a couple of weeks or so, then going back to that maintenance dose, which would be that 500 to 1,000 milligrams a day.

Lesley: So, that's 500 milligrams to 1,000 milligrams, in general, because I'd also imagine the curcumin that you're using, if it's highly bioavailable, you might need less, if it's not treated, you might need more. Would that be right?

Adrian: Yeah. Obviously, I'm generalising, and there's been lots of research around it. So, it does depend on the extract. So, while I'm giving these general numbers, it really does depend on what type of extract people are using. So, if I was to choose a curcumin extract or use a curcumin extract, I would be asking about has that curcumin extract been used for the treatment of pain? And what dosages did they use? And then, basically, go by that research.

Lesley: Yeah. And I'm sure people could check labels because that would be an indicator as to what would be the therapeutic dose. And as we talked about before, you don't want to underdose, or else you're wasting your time. 

Now, there's another herb that I absolutely love. It's called saffron. It's beautiful and there's just so much research coming through, I know, in the mental health area on this. And I also know you've been doing some work here, too, I believe. Do you see that might have some potential in chronic pain as well?

Adrian: Yeah, I've done a little bit of research on Saffron. Well, I'm exaggerating now. I've probably done six, seven, eight studies now...

Lesley: That's quite a bit.

Adrian: ... on saffron. So, in terms of saffron, from a pain perspective there's not a lot of research yet. There's some animal studies and preclinical studies showing that it may have an impact on pain. So, there's a couple of studies on neuropathic pain, there's been some studies on osteoarthritic pain, but they're animal studies. 

So, in terms of the human-based trials, not a lot. So, if I was to look at somebody who was coming in and they were experiencing chronic pain, I would definitely recommend curcumin above saffron from that perspective. But as we talked a bit about in the first part of the pain discussion, that's basically... many people with pain have depression and anxiety, and that's where saffron really comes to our head there. That's where saffron really has a therapeutic effect.

And there's been lots of studies done on saffron. And we've done studies on saffron for depression, we've done studies on saffron as an adjunct to antidepressants, like if you take saffron in addition to a pharmaceutical antidepressant, does it increase the effectiveness of that antidepressant? And we saw that it certainly did. So, if somebody's coming in who's having pain and also depression or anxiety, I'd highly recommend saffron as an option. And we've also done some trials for saffron for sleep. So, we've done two trials now for sleep, and again, we found that saffron has a really positive effect on sleep. So, again, that's another option for people.

Lesley: I find that really interesting because saffron seems to be filling in the gaps that curcumin's not, and curcumin's doing something a little bit different. Could you use the two together, for example, curcumin for more that immediate inflammation and all the things you talked about there? And if there is an issue with sleep and stress and mood associated with pain, you could take the saffron together?

Adrian: Yeah, it would make sense. You could definitely use the two together. And again, you are using that dosage of curcumin of 500 to 1,000 milligrams or somewhere around there. And then when it comes to saffron, the dosages are far smaller. So, people freak out a little bit when I talk about saffron because people know that saffron is extremely expensive. But the reality is that if you think about curcumin being 500 to 1,000 milligrams a day, saffron, you only use 15, even we've done studies on 14 milligrams to 28 to 30 milligrams a day. So, it's far less. It's 10 times less than curcumin. So, it's not that expensive because you're using a smaller dose.

So, with saffron, we've done studies of 14 milligrams to 30 milligrams a day is where people could be using it for. In the studies we did on sleep, one study we had people taking 14 milligrams twice a day, and then another study we actually got them to just take either 14 or 28 milligrams one hour before bed. And that was found to be effective. I'd be leaning more towards the 28 milligrams, or 28 to 30 milligrams is what I'd be leaning more towards, but certainly, that could work there.

And again, saffron, similar to curcumin, has multiple mechanisms of action. It impacts on neurotransmitters, it's anti-inflammatory, it's antioxidant, and in addition to that, we actually  just published a study where it also impacts on something known as heart rate variability. And a level of our heart rate variability is associated with general health, and stress, and general well-being. And you actually want to see an increase in heart rate variability. That means that's a positive thing, and saffron actually increased heart rate variability.

Lesley: Fascinating. I also found it interesting when when you taking about saffron helping antidepressants to work a little bit more effectively because I know in part one, Emma talked about the fact that with opiates, there seemed to be a shift amongst some doctors with the change of regulation in Australia on opiates, where some doctors were starting to recommend antidepressants in a chronic pain environment, which to me is really interesting because what you said about saffron making that work a little bit better, and then you've got the curcumin filling in those other gaps. It sounds like that might be a very interesting combination.

Adrian: Yeah definitely. You could certainly include the two. I mean, curcumin's another one. There was another study with curcumin as an adjunct. So, you can certainly use either of those as an adjunct to antidepressant medication.

Lesley: Great. Now we've talked about a couple of herbs, but we know there's a few vitamins that are very important. Michelle, we've been hearing a lot about the benefits of vitamin D. I know traditionally, back in the day, I was taught it was good for bones, and more recently, we know it's been very important for immunity as well. But what about pain? Does it play any role in the management of pain and inflammation?

Michelle: Yeah, it does, actually. Vitamin D is a pro-hormone and it's utilised throughout the body. I'm with you, too. We'd always think about vitamin D and bone health, but it's incredibly important for the musculoskeletal system and the nervous system as well. And so it works by supporting the muscle fibres and it primarily affects the faster and the stronger ones. So, it's been associated with improved proximal muscle strength, which I thought was really fascinating, and it modulates the neuro-excitability of the nerves.

And in part one, we spoke about neuropathic pain and nociception, and there's always an element of nociceptor hypersensitivity in all pain mechanisms, and so vitamin D does modulate that. And it also has a direct impact on the inflammatory pathways. So, it supports the prostaglandin pathways and it upregulates neuronal anti-inflammatory pathways as well. And it also has a direct impact on the cytokine pathways as well. So, it works on so many different elements to impact the inflammatory and the neuropathic aspect of both acute and chronic pain.

Lesley: Thanks for that. Another ingredient we've been hearing a lot about, particularly with our recent viral pandemic was quercetin. We know that quercetin works very closely with vitamin C, and there seems to be some science starting to suggest it might be useful for pain and inflammation. Michelle, what are your thoughts on quercetin?

Michelle: Yeah. So, it's been used a lot through animal studies and it's incredibly safe and cost-effective nutrient. It's part of the flavonoid family. So, it's abundant in fruits and vegetables, but we use it at a higher dose when we're using it therapeutically for acute and chronic pain. And it does seem to have some really significant emerging evidence using around the 500 milligram per day mark. And some people actually use it in between meals for both acute and chronic inflammation. And so it tends to have an impact on the inflammatory pain, neuropathic pain, and even cancer pain, which is a very multi-layered complex pain syndrome.

Lesley: So, quercetin and vitamin C together. And you were saying the dose of quercetin, what dose of vitamin C would you recommend with it?

Michelle: So, I love vitamin C, and I'd say it's very easy and accessible, a bit like quercetin. It's very cost-effective. And even as Emma mentioned before, 500 milligrams twice a day has been shown to be effective in chronic pain. And I often see that a lot in people with osteoarthritis or rheumatoid arthritis, that joint and muscular pain. Vitamin C tends to have a really significant impact. We use it sometimes in cancer, even at higher doses, intravenously, can impact people's well-being, but there's also some evidence to suggest that it supports that overall inflammatory response and makes people less sensitive.

So, Adrian was talking about that hypersensitivity, the perception of pain. And I wonder also whether vitamin C works on that perception of pain because it's such a global impact of decreasing the inflammation pathways of the body, but it also has an impact on cortisol pathways and stabilising the HPA axis, and then supporting overall brain health and mood.

Lesley: And we know that most people don't have enough fruit and vegetables. And also, if you cook up your vegetables, you can lose 100% of your vitamin C. So, people might think they've got a healthy diet. And it's surprising how low vitamin C really is in people’s body, isn't it?

Michelle: Yeah, absolutely. And stress uses it up as does smoking use it up. So, there is quite a cross correlation with people with chronic pain and smoking, so there's a higher increase of smoking in people with chronic pain and chronic depression, so we know that as well. 

And also other pollutants, too. We utilise our vitamin C to actually help protect us because it's such a significant antioxidant. So, if we're under any potential toxic load, whether it's toxic stress from our emotions, but also from environmental stressors like pesticides or perfumes, we're going to be using up our vitamin C stores as well. Let's face it, there's a lot of toxins out in the community on a day-to-day level. A diesel truck goes past and you're going to be using up your vitamin C, too. It’s a bit scary.

Lesley: Yeah. Lisa, throughout this podcast series we've made reference to the importance of inflammation resolution. So, resolving inflammation, not just dampening it down. I know you've been doing quite a lot of reading in this area. I think it'd be great to explore what does that mean? And what is the difference between reducing inflammation, resolving it? Why is it important for pain? And are there any particular ingredients that are starting to come up showing a lot of promise in this space?

Lisa: Sure. So, reducing inflammation is definitely something we still want to do with patients, but sometimes what we see with patients that have chronic inflammatory conditions is that their ability to reduce inflammation is actually dysregulated. So, the research is now saying that we need to look at chronic inflammatory conditions through the lens of a failed resolution phase. They're not actually resolving that inflammation. They're stuck in this cycle where the immune system's trying to resolve the inflammation, but it's just not actually able to do that properly. So, that really drives the chronic disease and we see this failed resolution in a lot of conditions, like autoimmune disease, chronic pain conditions, cardiovascular disease, and so on.

So, in terms of what we can do is, essentially, we need to fix that switch that occurs from a pro-inflammatory state to an anti-inflammatory state because that's what's broken. And essentially, the pathways are blunted, is what the research shows. And that can be due to things like obesity, metabolic syndrome, nutritional deficiencies tend to drive those pathways becoming a little bit blunted.

So, there are these things called specialised pro-resolving mediators, and we're going to call them SPMs for short and basically, they're derived from our omega-3 fatty acids, and we produce them naturally in that acute inflammatory phase. But we only do that when we're healthy. So, what we've found is that people that have chronic inflammatory conditions are not able to actually make enough of those SPMs, the process becomes dysregulated. And this is where supplementation has been shown to be quite helpful. So, what SPMs do is their job is to actually resolve inflammation and pain by reprogramming those immune cells for that repair process to take place.

So, they have been trialled in a couple of human clinical studies because they're relatively new. There's been a lot of preclinical work done. They have been trialled in adults who had chronic pain for about three months, and they were otherwise healthy, so like a lot of the patients that we see. So, they were given the SPMs for a month and they experienced an improvement in their quality of life, better mood, and most importantly, a reduction in pain at that one-month mark. So, we're looking at a dose of about 250 milligrams, but probably need to be taking them for a little bit longer is my experience in clinic.

There's been another follow-up trial where they actually utilised SPMs in conjunction with curcumin, which is really, really interesting because of all the things, obviously, that Adrian talked about, but also because the curcumin, as we know, is anti-inflammatory, but then you're combining it with the SPM that is there to resolve that inflammation. So, really nice combination. And again, these individuals took it for two months, experienced a reduction in pain, improvement in mood, and improvement in quality of life as well. So, they're pretty exciting, I think, for patients that are dealing with chronic pain conditions.

Lesley: It's such a new area, isn't it? Specialised pro-resolving mediators. It's a mouthful, SPMs. But it makes sense that in a healthy response, you have inflammation and then eventually, something kicks in to just cut it off and say, "Right. Done its job, finish, resolve, let's go on.” And it seems to me like in chronic pain, that shutoff valve never happens, it never really kicks in. So, I think what you've been saying is that these SPMs might be able to help with that shutoff valve to just close things off like they should have been.

Lisa: Absolutely. That's right.

Lesley: Great. So, Lisa, how long does it take before SPMs kick in and people start to notice a difference?

Lisa: Oh, that's a really good question. So, we are seeing an improvement within a month in terms of pain, but I do feel, having used them clinically, they do need to be taken longer. And they're relatively safe, they're similar in terms of safety profile to the omega-3s, and we know they can be taken long term. So, I've been looking along those lines. And I think when we use the SPMs and we are applying dietary and lifestyle changes, we're reducing weight, changing the diet, then we see that our own body's production of SPMs becomes more efficient, and that's probably when they'll notice even more of a reduction of pain and then can wean off.

Lesley: Right, that makes sense. So, you're helping the body while it's in need and then as the body starts to repair and make its own, you can just wean them off.

Lisa: Yeah, exactly.

Lesley: So, I've been hearing a lot about PEA.

Lisa: Yes.

Lesley: That's another new one, new kid on the block. And I hear about these incredible stories where for some people, it just seems to change their world. Not everyone, no ingredient does, but for those ones that this seems to work for, it just seems to really make such a difference, particularly, obviously, we're talking about chronic pain here. Can you tell us a little bit more about PEA? What is it? How does it work? And does it actually reduce pain and inflammation in your experience?

Lisa: Absolutely. So, PEA is such a hardworking compound, I think, because it exerts its effects in multiple ways. And again, it's another one that we produce when we are in pain and inflamed. It's produced in the lipid bilayer of our cells as a protective repair mechanism initiated by the body. So, what it does is it stops mast cells from degranulating. And what we know about mast cells is when they spit open, they release things like histamine and serotonin, which increase pain hypersensitivity. So, by reducing that, obviously, that assists with reducing pain.

PEA also activates different enzymes or different receptors that basically reduce the expression of enzymes involved with inflammation such as COX-2. So, it stops them from basically promoting that inflammatory response. And then thirdly, it also has what is called an entourage effect. So, a helping effect where it indirectly activates receptors such as the cannabinoid receptors, but it's doing this indirectly, again, to promote that pain relief. So, it's pretty clever in the way that it works. And not just one action, multiple.

Lesley: So, with PEA, how would people use it? What's the dose? And how safe is it?

Lisa: So, PEA is incredibly safe as a supplement. As I said, we produce it ourselves, but we often need much higher levels in supplemental form. And we've also found with the research that when someone's in chronic pain and they're inflamed, again, it's that dysregulated response where they're not making enough, so that's where supplementation can help. Now, I really, really love it. I find it great in clinic for chronic pelvic pain, endometriosis, dysmenorrhoea.

And there's a great meta-analysis of four trials showing that it really, really helped to reduce chronic pelvic pain in endometriosis and that dysmenorrhoea. It's also been trialled for vulvodynia in combination with a TENS machine, bladder pain, burning mouth syndrome, sciatica, migraines, including paediatric migraines. So, for paediatric migraines, the dose is a little bit lower, it's 400 milligrams, whereas, for those other conditions, we're looking at a slightly higher dose of 600 milligrams twice a day.

Lesley: And in terms of safety, are you picking up anything?

Lisa: No. It's super, super safe. I think there's very, very mild side effects. Not really noted, but one paper I read said that the patient felt like they were floating, which...

Lesley: Not a bad thing.

Lisa: ...doesn't sound so bad. That's right.

Lesley: And when you say the cannabinoid receptors, obviously, people's ears just spring up to go, "Oh, that sounds interesting." Is there any addictive element to this as well?

Lisa: No. Not as far as I can see from the research, no.

Lesley: Okay, great. So, you would use this as an acute treatment, or how does this fit into your practice?

Lisa: No. Okay, so with the research, we are looking at about three months duration for things like chronic pelvic pain, but you can actually use it for much, much longer, for up to a year. There's research showing that it's quite safe.

And an interesting backup to what we saw with the research on pelvic pain and endometriosis is that in another study, when women took it for nine months, the pain improved at three months, but their sexual function, actually, they reported an improvement in sexual function at nine months. So, I think that's really clinically significant for us to know, okay, the longer we take it is also going to improve quality of life and things like that, too.

Lesley: Great. Now, I need to talk to Emma about one of my favourite components, omega-3 fatty acids. The amount of research on omega-3 fatty acids, there's tens of thousands of research papers on this. It must have a role here. Emma, can you tell us a little bit about the role of omega-3s here? What does it do? And how do you use it? And what would be the doses as well?

Emma: Yeah, sure. I'd love to. It's such a fascinating area, this one. And as you said, the research is just never-ending. It's amazing. 

If we think about the mechanisms at play of how they actually work, there's two. The first mechanism, omega-3s compete with arachidonic acid for inclusion in cyclooxygenase and lipoxygenase pathways. So, this results in anti-inflammatory mediators. Things like the resolvins that Lisa was just talking about, protectants, they also produce an inflammatory mediator, eicosanoids, but they're not that inflammatory. So, that's their first mechanism.

The second is that omega-3s are transported through the cell membrane and they directly influence the transcription factors that play a key role in inflammation. So, they've got that dual mechanism, which, I think, harmonise really nicely in this anti-inflammatory space, but the research is fascinating.

And I really want to talk about the UK Biobank population-based cohort study. It's 500,000 people between the ages of 40 and 69. And this is a lot of the ages that we would be seeing clinically, this age. So, 32% of the people were actually taking fish oils at baseline. And researchers have since studied all the epidemiological data and there's been some really significant outcomes. So, fish oil supplements were associated with a 13% lower risk for developing dementia and also an 18% lower risk of developing diabetes.

The Biobank data also showed that people with chronic, widespread pain actually experience premature mortality, usually related to cardiovascular, cancer, or respiratory causes. So, that is just so impactful right there. But I think the analgesic action of omega-3s is obviously due to that anti-inflammatory action that I spoke about.

But I found a meta-analysis on the analgesic effects of omega-3s for joint pain and this was super interesting. So, after four months of supplementing with omegas, the patients reported a lower intensity of their joint pain, less morning joint stiffness, but what I loved about this was there was a noticeable reduction in their non-steroidal anti-inflammatory pain medication use.

Lesley: Wow.

Emma: Yeah.

Lesley: Wow.

Emma: So, that in itself is going to have benefits. But I also think omega-3s have the effect of increasing blood flow to the cells. They're bringing more oxygen, more nutrients to the cells that need that support, and that effect on cell functioning, I think, is something that maybe we don't talk about enough, but omega-3s can really help in this way.

Let's delve into doses. There's so much here. One thing I did love to see was the 2019 Practice Guidelines from the International Society for Nutritional Psychiatry on omega-3s for major depressive disorder. And they recommended a 2 to 1 ratio of EPA to DHA and a net daily intake of one to two grams of EPA per day. So, it's just so great to see the practice guidelines internationally being altered and omega-3s getting recognition in that space.
But when we are looking at things like rheumatoid arthritis, the clinical data is there. Therapeutic doses that we need for pain need to be high, but from just a health span disease prevention perspective, you would look at doses around 1,000 milligrams a day, ideally, around 750 milligrams of EPA and around 250 of DHA.

But looking at the research on reducing rheumatoid arthritis pain, this is where it's interesting because this pain is just so debilitating. We have so many people suffering from rheumatoid arthritis, so when you're looking at the doses that the research is saying is effective, the most benefit is between three to six grams of omega-3s a day, which is probably a bit higher than what most people might think. But as we've spoken about, in order to get a therapeutic outcome that's beneficial, we have to hit these therapeutic doses. So, rheumatoid arthritis pains, we're looking at three to six grams per day.

There was another study that looked at rheumatoid arthritis as well and that came up with at least 2.7 grams of combined EPA per day for more than 3 months. This isn't fast. Like SPMs or EPA can be really fast, this is not fast. But this study as well, the patients used less of their non-steroidal anti-inflammatory drugs and I think that that is a brilliant outcome. 

So, essentially, a key takeaway on doses is, for rheumatoid arthritis, you can really safely advise your patients that taking at least a three-gram dose of combined omegas is going to be beneficial, but you have to tell patients we need to do this for at least three months.

Lesley: One of the things that I loved about what you said with omega-3s is the fact that you're getting so much bang for your buck, really, aren’t you? You're getting reductions in cardiovascular disease, you're looking at mental health issues that are going to be responding here as well. There was a whole bunch of things you mentioned before as well as effects on pain. So, I guess, again, it's like one of those poly-pills. It just seems to do so many things. And from a safety perspective, are there any issues that you know of, or how do you advise your patients when they use omega-3s?

Emma: Well, I always tell them to stop their omegas before they do any surgery. But essentially, these doses are very safe. Yeah.

Lesley: Okay. No, that's great. And I'm assuming add the Mediterranean diet to this, and magic.

Emma: Absolutely. That's where the magic starts to happen. When you combine therapeutically indicated diet, lifestyle, nutrients, that's where the magic happens.

Lesley: Yeah. Great. Now, there is another herb that I know a lot of people use. We've talked about curcumin before, we've talked about saffron. This is one that’s got a European background, and that's boswellia. And I know there's been a bit of research on that in reducing pain and inflammation. Can you tell us a bit more about boswellia?

Emma: Yeah. Well, this herb has such a historical use. It's the same genus that frankincense comes from. So, it's going back a long way. It is anti-inflammatory, anti-arthritic and analgesic, all of those things, which is such a great combination. But when we are looking at the research, 35% of men and women over the age of 55 suffer from osteoarthritis. That's a lot of people. And 55 isn't that old, can I just say? Many of these people will be taking non-steroidal anti-inflammatory medications, but unfortunately, those medications can have significant side effects. And my personal opinion is that the best strategy is to use the lowest dose of them that's needed.

But research shows that taking 300 milligrams of boswellia per day actually reduces the amount of non-steroidal anti-inflammatory drugs needed as well as improving pain and mobility. Other research shows that between 100 to 250 milligrams per day for a period of 4 weeks demonstrated the clinical benefits of improved joint function, reduced pain, and stiffness. Now if you think about getting out of bed in the morning for somebody that has osteoarthritis, that's going to be a hell of a lot better on their quality of life.

Then finally, a meta-analysis of trials with patients with knee osteoarthritis showed a dose of boswellia between 100 to 250 milligrams for 1 to 3 months moderately, not mildly, moderately reduces pain and improves function when compared to placebo. So, look, overall I'd say boswellia is not used enough. I would say that it is so well indicated for osteoarthritic conditions at a daily dose of around 200 milligrams for a minimum of, I would say, 8 weeks.

Lesley: And I know there's been a bit of research on boswellia also for back pain as well, chronic back pain, which is, again, a really big problem in our community, isn't it?

Emma: Yeah, absolutely. And it has a very good safety profile.

Lesley: Yeah. Fantastic. So, the thing that I am finding really interesting is we've been talking about different components for different pain, and I think that's really important to get right, how so many of these ingredients have got multiple activities as well. Often, they take time. There's a few that work quickly, but often they take a little bit of time, and that they're safe. And, Em, what you said before, you've been telling me about a number of things now where we’ve been able to reduce medication use, which is such an important factor.

Emma, we know that the use of non-steroidal anti-inflammatory drugs can cause gastric irritation and bleeding, people presenting to even emergency departments with significant bleeding. So, they've got a place, but there's also a safety issue that people forget about. And if there's a way to reduce their reliance on those things into things that are going to be safer for the long term, it's fantastic.

Emma: Yeah, absolutely. And look, clinically, what I see is that patients are often not realising that the epigastric pain they're suffering from is because of the medication. So, often, they've been doing that and experiencing that pain for quite a long time before it's actually picked up on. So, I really love the concept of having strategic herbs like boswellia that can really help in that case.

Lesley: And one of the things I know you use in your practice is a pain diary because you were just talking about patients reporting their own symptoms and monitoring themselves and you're helping them to recognise that. How do you use that?

Emma: Yeah, I find this so incredibly helpful. So, they just literally need to fill it out on a piece of paper that is like a pre-formatted sheet, and every day they need to rate their pain, how it's impacted their day, what pain relief they've needed, so what pharmaceutical pain relief they've needed, as well as what non-pharmaceutical pain relief they've needed, like wheat packs, TENS machines, a bath, those kind of things. And the beauty of this is that it really helps the patient to connect with when their pain flares and when it's better, for a start, and they can also see their progress over time. Because as we all know, it's very easy for patients to come back and not realise the progress that they've made. So, in order for us to help them understand their progress and really celebrate that, a pain diary. It's so cost-effective, it's easy to do, and it's a really helpful clinical tool.

Lesley: And I can imagine it helps people feel self-empowered, that self-efficacy that I know Adrian talked about in part one. That would all be part of that, too.

Emma: Yeah, absolutely.

Lesley: Which brings me to Michelle because I'd imagine you use tools like these in your practice as well and the importance of lifestyle factors, and how that influences everything, too. Can you tell us a little bit about how you roll in that conversation about lifestyle factors, and what are those key things that you tell your patients?

Michelle: Yeah, it's a great question and I think overall, we've spoken in part one and part two about just the importance of a holistic approach to chronic pain and chronic inflammation. And getting people really engaged in and empowered into their own health journey is a really critical part of dealing with this long term and very complex problem that affects so many people.

And so, Emma mentioned the Mediterranean diet and what an incredible anti-inflammatory effect your diet can have and so many aspects of removing pro-inflammatory foods from our diet, things like alcohol, dairy in some people. Sugar is highly inflammatory for lots of people, and also the impact of carrying excessive weight around the middle, which, as we know, creates inflammatory responses and is a pro-oxidant in its own right.
And so looking at overall aspects of exercise is a really critical part of lifestyle medicine. So, there was a huge meta-analysis on lower back pain that came out a couple of years ago about the importance of exercise. And exercise is probably the primary prescription that needs to be given for people with lower back pain.

So, diet as we know in the naturopathic world and probably more of the holistic integrative world is so important, but in mainstream general practice, a prescription for exercise is probably the primary way the RACGP, which is the college, talks about dealing with chronic lower back pain. So, exercise is profound in terms of its anti-inflammatory effect, its impact upon mood and sleep, and all of the empowering and self-image and self-esteem impacts that exercise has as well. So, that's one very important factor for lifestyle.

The other thing is social health. So, often with chronic pain, and we talked about the stigma of chronic pain in part one, but also looking at the impact of loneliness and social well-being for people with chronic pain. So, encouraging support groups either online or in person can be great, and putting them together in your clinic if you do service people with chronic inflammation and chronic pain a lot has been shown to be very impactful and very effective at supporting that sense of connection and social support that's very, very important in bringing lifestyle medicine together. So, that social isolation and that stigma is probably one of the leading things that make people feel disempowered and held back from the long-term solution.

And also, we need something cost-effective, too. So, group work and social connection seems to be very cost-effective. And so I know in my local area, they have a walking group for people with arthritis, be it rheumatoid or osteo or whatever that is. And then they meet for a coffee and they go for a walk and they get the benefit of doing that. But I should tell them not to have coffee and to have rosemary tea instead. And so I'll put my two bob's worth into it as well.

But stress management is really important. We spoke so much about the impact of chronic pain on mental health, but also looking at stress in general. So, there's a lot of research on the impact of stress in surgery and cancer, in addition to its impact on depression and mental health aspects of coping with something like that. But stress as a load on people is really important to consider.

We spoke a little bit about vitamin C and how it's almost like an anti-stressor agent. It's such a powerful antioxidant and so it works on that HPA axis and reducing down stress of all causes, but stress of things like excessive alcohol, excessive caffeine, excessive smoking, sedentary behaviour, chronic poor sleep or chronic under-sleep, under-functioning. Under-functioning in terms of brain function and passion, and engagement in life is also a stressor as well that needs to be looked at.

And then there's things like chronic infections and the impacts of surgery and chronic surgeries and anaesthetics and medications. All need to be seen in a bucket of a stressor. And allowing patients to see that as a collective can see how they can minimise those things over time, little bit by little bit, particularly if they're trying to wean off significant medications like opioids or anti-inflammatories, as Emma mentioned. And so that improves the overall basis of things.

And then teaching people how to communicate to other people about their chronic health can actually help destigmatise it. So, it's important as a clinician to believe patients. Remember the definition of pain is that it's a subjective experience, and so it really is about that person's experience of pain and not our judgment on that person's subjective experience of pain. That's so important for maintaining the rapport and the empathy that's required long term, and so that then they can then hand over that responsibility and empowerment. So, lifestyle factor is just so critical, and taking people long term through what is there to be offered so that we can unravel that chronic neurological change that is associated with chronic pain over the long term.

Lesley: One of the things that I've been finding really interesting in this particular episode is how a number of the ingredients you've talked about, say saffron, omega-3 fatty acids, and curcumin not just have an effect on the physicality of the body, but also mentally, and how you've got that cycle of mental health affecting physical, physical health affecting mental, and all the things that you've talked about here. And it's just uncanny or by grand design that they seem to be hitting on a number of these things in the same component, which is just fascinating.

Lisa, tell me, as a naturopath, I'm sure you get to see people like these all the time, and maybe they've tried everything before, and you're going to give them a fresh approach, and as a naturopath, teach them a little bit more about themselves and empower them and use some of the tools in the toolkit that we've talked about today. How do you manage those people? And what do you think about a collaborative care approach as well? Because it sounds to me like it's so complex.

Lisa: Absolutely. So, in my clinic, collaboration is incredibly important and I tend to do that with pretty much every client that comes in. They will get a referral, first of all, to the GP to assess for…to get a nice baseline for where they're sitting. We've talked today about vitamin D, for example, being really important with regards to sleep and pain perception and so on, but also as a source of referrals to other practitioners. So, for example, a psychologist. 
Again, we've heard just how important mental health is with regards to management of pain, and we know that there's higher levels of suicidality and so on when someone is under chronic pain. So, I love to work with a psychologist, not only for talking about and chatting through feelings of loneliness and isolation, but also to learn techniques to assist with managing that chronic pain.

Another referral I love is a musculoskeletal therapist. So, for example, a chiropractor or a physiotherapist, I find really, really useful to assist my patients with resolving their pain. And often for some patients, there is that musculoskeletal imbalance that's contributed to their condition in the first place. And if we don't understand and treat that underlying cause, it will happen again. And again, for women who have chronic pelvic pain, a women's physio is really great there.

So, the research shows that when we collaborate with other health practitioners, the patient actually gets a better result. Research done with collaborating for patients that have chronic pain shows that they actually reduce their pain and they have better mood. So, it's a really important thing to do, I think, as a practitioner to collaborate for our patient.

Lesley: So, I'd imagine as a naturopath as well, building those connections, building that trust, they trust you, you trust them, you found the right people and they know how you think, you know how they think, would be so important.

Lisa: Absolutely. And we're all working together as a team for our client.

Lesley: Yeah, that makes sense. Look, thank you, everybody, today. We've, again, covered a lot of ground. We talked about the very popular curcumin, and we talked about saffron, we've talked about vitamin D, quercetin, vitamin C. I think for a lot of listers, they've hopefully learnt something new about specialised pro-resolving mediators, SPMs, as well as PEA, which are fairly new, I think, to a lot of people. Omega-3s, we've known about for a long time, but the fact that it can also play a role here, and the doses that are required to make sure the doses are appropriate.

And I think, Em, you mentioned in rheumatoid arthritis, you'll have to go pretty high, three to six grams. Getting that right is going to be important. Boswellia, of course, pain diaries, collaboration, lifestyle, throw it all together and I think we've got really something important to be offering here, people, particularly as they are going on that rollercoaster of not knowing what to do when they start to spiral and how we can intervene. So, thank you, everybody. It's been an absolute pleasure talking to you today.

Emma: Thanks so much, Lesley.

Lisa: Thanks, Lesley.

Michelle: Thank you.

Adrian: Thanks, Lesley.

Lesley: This was the second part of our two-part series on chronic pain and inflammation. So, if you missed the first part, be sure to listen to it today as we discuss the landscape of pain and chronic inflammation from the perspectives of our four ambassadors. 

You've been listening to FX Medicine, and I'm Professor Lesley Braun. Subscribe to us on your favourite podcast app and follow us on social media to make sure you never miss an episode. Thanks for listening, and we'll talk to you soon.


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