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Nutritional Interventions in the Management of Fibromyalgia Syndrome

Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Unit of Clinical Nutrition, Careggi University Hospital, 50134 Florence, Italy
Author to whom correspondence should be addressed.
Nutrients 2020, 12(9), 2525;
Submission received: 4 August 2020 / Revised: 13 August 2020 / Accepted: 19 August 2020 / Published: 20 August 2020
(This article belongs to the Section Clinical Nutrition)


Fibromyalgia (FM) is a multifactorial syndrome of unknown etiology, characterized by widespread chronic pain and various somatic and psychological manifestations. The management of FM requires a multidisciplinary approach combining both pharmacological and nonpharmacological strategies. Among nonpharmacological strategies, growing evidence suggests a potential beneficial role for nutrition. This review summarizes the possible relationship between FM and nutrition, exploring the available evidence on the effect of dietary supplements and dietary interventions in these patients. Analysis of the literature has shown that the role of dietary supplements remains controversial, although clinical trials with vitamin D, magnesium, iron and probiotics’ supplementation show promising results. With regard to dietary interventions, the administration of olive oil, the replacement diet with ancient grains, low-calorie diets, the low FODMAPs diet, the gluten-free diet, the monosodium glutamate and aspartame-free diet, vegetarian diets as well as the Mediterranean diet all appear to be effective in reducing the FM symptoms. These results may suggest that weight loss, together with the psychosomatic component of the disease, should be taken into account. Therefore, although dietary aspects appear to be a promising complementary approach to the treatment of FM, further research is needed to provide the most effective strategies for the management of FM.

1. Introduction

Fibromyalgia (FM) is a complex, multifactorial syndrome characterized by widespread chronic pain and a constellation of somatic and psychological manifestations, including fatigue, joint stiffness, sleep disorders, depression, anxiety, gastrointestinal and cognitive disorders [1,2,3]. Diagnostic criteria have recently been updated by the American College of Rheumatology and, using these criteria, FM is now recognized as one of the most common chronic pain conditions and the second most common cause of visits to rheumatologists after osteoarthritis [4]. It can occur at any age with a prevalence of 2–8% in the general adult population, and is more common in women than men, with a ratio of 2:1 [5,6]. Despite progress in understanding the mechanisms involved, the etiology of FM is still unknown, and the pathophysiology uncertain. Various evidence supports the hypothesis that FM is a “central pain disorder”, with alterations in central nervous system function leading to increased nociceptive processing [7,8]. Furthermore, recent evidence suggests that low-grade systemic inflammation, a preponderance of prooxidative status and an insufficient antioxidant capacity, could contribute to the development of the disease, reducing the pain threshold and inducing fatigue and mood disorders [9,10]. FM shows strong family aggregation and, although this may be due to shared environmental or behavioural influences, twin studies have revealed that genetic variants and hereditary mechanisms contribute to 50% of the risk of developing chronic pain and related conditions in FM [11,12,13]. Currently, no predisposing gene has been found, but it has been reported that several environmental factors, such as psychological and physical trauma or certain infections, can trigger development and influence the severity of FM through epigenetic mechanisms [14,15]. It is believed that there is a bidirectional temporal association between some psychological stressors and FM, with an increased risk of developing each other, suggesting a potential shared pathophysiological mechanism underlying these different conditions [16].
To date, optimal management of FM requires a timely diagnosis, together with a comprehensive assessment of pain, function and psychosocial context. Effective treatment is not available, and experts recommend nonpharmacological therapy as a first-line strategy, with the pharmacological option to be chosen only in case of lack of effect [17,18]. Among the nonpharmacological treatment options, nutrition has shown increasing interest in the literature in recent years [19,20,21]. This review aims to summarise the possible relationship between FM and nutrition, exploring the role of nutrients, foods and dietary patterns in FM syndrome.

2. Nutritional Supplementation and Fibromyalgia

An imbalance of dietary components, including minerals and vitamins, can play a critical role in the development of FM. A survey conducted by Arranz and colleagues [22] revealed that 73% of the subjects affected by FM are users of nutritional supplements, and 61% of these became users after the onset of the disease. A recent meta-analysis showed little evidence to support the hypothesis that vitamin and mineral deficiencies could play a significant role in the development of FM, or that the use of nutritional supplements could be effective in these patients [23]. However, some intervention studies evaluating the possible effects of nutritional supplements on FM patients have been published to date and are reviewed in Table 1.

2.1. Vitamin D

Some evidence suggests that vitamin D supplementation should be considered in the management of FM in light of the fact that about 40% of FM subjects have been reported with vitamin D deficiency [37]. In addition, several studies have suggested an association between low serum vitamin D levels and chronic pain, depression and anxiety in FM patients [38,39]. The first study investigating the effect of vitamin D supplementation on FM subjects was conducted by Arnold and colleagues in 2008 [25]. Ninety FM patients with mild to moderate vitamin D deficiency were randomly assigned to receive 50,000 units of cholecalciferol (vitamin D3) per week compared with a placebo. After 8 weeks of intervention, the treated group showed a significant improvement in FM scores, in contrast to the placebo group [25]. Subsequently, other studies were performed to evaluate the effect of vitamin D supplementation in FM patients [26,27,28,29,30,31]. Although in a limited sample of participants, all of these studies reported a beneficial effect of vitamin D supplementation. Only the study by Warner et al. reported inconclusive results regarding the benefits on FM symptoms [24]. However, all authors stressed the importance of testing serum vitamin D levels and recommend supplementation when risk factors for vitamin D deficiency are present.

2.2. Vitamin C and Vitamin E

Antioxidant vitamins such as vitamin C and vitamin E can play a beneficial role in the management of certain typical symptoms of FM, since they are useful for preserving the cerebellar functions, memory, emotive responses as well as muscle function [40]. However, there are currently no consistent studies in the literature. A recent meta-analysis reported lower levels of vitamin E in FM patients than in healthy controls, although this difference disappeared when low quality studies were excluded from the analysis [23]. In addition, treatment with vitamin C and E combined with or without exercise compared to exercise only in 32 women with FM over a 12 week period did not show a statistically significant improvement in FM symptoms, although both interventions resulted in significantly higher serum levels of vitamin A, C and E [32].

2.3. Minerals

Regarding the mineral status, several studies have shown a decrease in intracellular magnesium content in FM patients [41,42]. Magnesium deficiencies were largely associated with low-grade inflammation, muscle weakness and paresthesia, which are typical symptoms of FM [21]. A recent study has shown that low dietary magnesium intake is correlated with worsening pain threshold parameters in FM patients [43]. Magnesium has always been considered the nonpharmacological supplement with the highest potential for FM [44]; however, so far, only two clinical trials have been performed in FM patients. The first study investigating the effect of magnesium combined with malic acid supplementation was performed in 1995 by Russell and colleagues, showing little or no effect on pain or depression in 24 women with FM when using low doses of supplementation [33]. However, with increased dose and a longer duration of treatment, a significant improvement in pain and tenderness was reported [33]. The second study tested the effect of treatment with magnesium citrate in combination with amitriptyline versus amitriptyline in 60 female FM subjects, showing that amitriptyline and magnesium supplementation were more effective in all measured outcomes than amitriptyline alone [34].
With regard to other minerals, some studies indicated a potential link between iron deficiency and FM [45,46,47]; however, only one study evaluated the effect of iron supplementation on FM symptoms, fatigue and iron status of 81 FM subjects, showing an overall improvement only in the treated group [35].

2.4. Probiotics

Increasing evidence suggests that FM patients may present altered microbiota, with the abundance of different taxa selectively correlated with disease-related symptoms [48]. This has led researchers to hypothesize a potential beneficial use of probiotics in the treatment of FM. A pilot study to investigate the effect of a 7 week supplementation with a multispecies probiotic showed improved cognition, particularly impulsive choice and decision-making, in 40 subjects diagnosed with FM [36]. On the other hand, no other beneficial effects were observed in self-reported pain, quality of life, depression or anxiety [36].

2.5. Other Substances

Several studies have reported an association between amino acid deficiencies such as valine, leucine, isoleucine and tryptophan and FM symptoms [49,50]. However, to date, no intervention studies have been carried out to test the effect of a supplementation with these elements. Furthermore, some studies have reported some potential benefits in FM patients from botanical or antioxidant supplements, although the evidence to support these substances is very weak. Several nutritional supplements such as Chlorella pyreinoidosa, cellfood, coenzyme Q10, Ginkgo biloba, ascorbigen, L-carnitine, S-adenosylmethionine, creatine and melatonin have shown some benefits for FM patients, improving symptoms such as muscle pain, fatigue, morning stiffness and quality of life [19]. Although patients frequently experience several positive effects from supplementations, there is insufficient evidence to recommend their use in the clinical practice.

3. Dietary Interventions and Fibromyalgia

Several dietary approaches have been proposed with the aim of reducing the symptomatology of FM (Table 2). The proposed nutritional strategies have been usually aimed to correct any nutritional deficiencies or to interfere with the different pathophysiological pathways supposed to be involved in the occurrence of FM.

3.1. Olive Oil

Extra-virgin olive oil (EVOO) is characterized by a high concentration of phenolic compounds. The countless health benefits of the EVOO are mainly due to its antioxidant activity, which is linked to its ability to protect DNA, proteins and lipids from damage caused by exposure to reactive oxygen species (ROS), which in turn are increased in FM patients [51]. A clinical trial investigated the effect of 50 mL/die of EVOO compared to refined olive oil in 23 female FM subjects. After 3 weeks of intervention, the authors reported a statistically significant improvement in protein carbonylation, lipid peroxidation, FIQ and mental health status after the intervention with EVOO [51]. Recently, the same research group reported similar beneficial effects of EVOO on several cardiovascular risk markers of 30 FM women, concluding that EVOO can protect women with FM against cardiovascular disease, thus proving to be a valuable therapeutic support in patients with FM [52].

3.2. Ancient Grain Products

In recent years, interest in ancient grains such as Khorasan wheat has been steadily increasing due to their beneficial effect on various pathological conditions [73,74]. The positive effect on health status seems to be due to the higher content of macro- and microelements, in particular magnesium, phosphorus, potassium, selenium and zinc, as well as carotenoids and polyphenols, compared to modern wheat [75]. Our group recently studied the effect of a replacement diet with cereal products based on ancient Khorasan wheat compared to the modern variety “Palesio” on the symptoms and quality of life of 20 patients with FM [53]. After 8 weeks, participants reported an overall improvement in the severity of FM-related symptoms, including widespread self-reported body pain, daytime sleepiness, fatigue and tiredness, resulting in an improvement in the impact of the disease on daily activities, with a greater positive effect after the intervention with Khorasan.

3.3. Monosodium Glutamate and Aspartame-Free Diet

Monosodium glutamate (MSG) and aspartame may act as excitotoxin molecules in organisms, acting as excitatory neurotransmitters, and may lead to neurotoxicity if used in excess [76]. Two case series on a total of 6 FM patients reported an overall improvement in FM symptoms such as chronic pain, fatigue, sleep and cognitive function after several months of aspartame-free or MSG plus aspartame-free diet [76,77]. A 30% remission of symptoms after an excitotoxin elimination diet was also observed in a sample of 46 patients with FM and irritable bowel syndrome (IBS) [54]. Interestingly, the MSG challenge led to a significant return of symptoms, a worsening of FM severity and a decrease in quality of life in almost all patients [54]. On the other hand, a total of 36 women with FM reported no significant differences in pain after a 12 week elimination of dietary MSG and aspartame, suggesting that discontinuation of dietary MSG and aspartame did not improve the symptoms of FM [55].

3.4. Gluten-Free Diet

FM patients often have gastrointestinal symptoms that significantly overlap with various gluten-related disorders such as nausea, abdominal pain, fatigue, tiredness, chronic pain and mood disturbance, suggesting a possible coexistence of noncoeliac gluten sensitivity in such patients [18]. This has led many investigators to hypothesize that a gluten-free diet could be beneficial for patients with FM. A pilot study investigating the clinical impact of a 1 year gluten-free diet in a small sample of 7 patients with coeliac disease, IBS and FM, revealed an overall improvement of pain symptoms, quality of life, cognitive function as well as of tissue transglutaminase serum levels [56]. The same research group investigated the effect of a 1 year gluten-free diet on 97 women with FM and IBS with or without lymphocytic enteritis, showing a slight but significant improvement in both IBS-related symptoms (chronic abdominal pain, changes in intestinal habit, bloating) and FM-related symptoms (chronic widespread pain, generalized tender points, fatigue and restless sleep) in the subgroup of lymphocytic enteritis [57]. Similar results were obtained in a 16.4 month gluten-free intervention on 20 FM patients without coeliac disease [58]. In addition, Slim and colleagues recently performed a 6 month intervention trial to study the effect of a gluten-free diet versus a low-calorie diet in 75 patients with FM experiencing gluten sensitivity-like symptoms [59]. Authors found that both dietary interventions resulted in beneficial effects on symptoms concluding that the gluten-free diet was not superior to the low-calorie diet in FM subjects with symptoms similar to gluten sensitivity [59].

3.5. Low-FODMAPs Diet

FODMAPs (Fermentable Oligo-Di-Mono-saccharides And Polyols) are poorly absorbed short-chain carbohydrates including lactose, free fructose, polyols, fructans and galacto-oligosaccharides. The low-FODMAPS diet has shown significant benefits in the treatment of IBS [78]. Since 70% of FM patients suffer from IBS [79], it has been hypothesized that the low-FODMAPs diet could be beneficial for FM subjects [60,61]. A 4 week intervention trial of 38 women with FM showed a significant reduction in gastrointestinal disorders and FM symptoms, including pain scores [60], as well as a reduction in body weight and waist circumference [61].

3.6. Low-Calorie Diet

It is known that high body mass index is associated with a number of disabling musculoskeletal conditions, suggesting that obesity may worsen symptoms of FM [62]. The most commonly used dietary strategy to reduce body weight is certainly the caloric restriction. In a pilot study, Shapiro and colleagues tested the effect of a low-calorie diet on 42 patients with FM, showing that after 20 weeks of intervention, participants reported a 4.4% reduction in body weight, along with an improvement in pain symptoms, body satisfaction and quality of life [62]. Similar results were obtained years later by Senna et al. [63], analyzing the effect of a 6 month hypocaloric diet on 83 FM subjects. Patients who lost weight reported lower interleukin-6 and C-reactive protein levels than controls, as well as lower depression and improved sleep and quality of life [63]. As a result, a more aggressive low-calorie diet for 12–16 weeks in 123 obese FM subjects led to improved pain symptoms, sleep pattern and depression, along with increased levels of anti-inflammatory cytokine interleukin-10 [64].

3.7. Vegetarian Diet

Vegetarian diets are characterized by large amounts of plant foods rich in fiber, vitamins, minerals and antioxidant elements, leading to the hypothesis that this dietary pattern may exert pain-relieving effects in FM patients, due to its anti-inflammatory properties and absence (or reduction) of animal proteins [80,81]. The first study testing the effect of a vegetarian diet on FM patients was performed in 1993 on a small sample of 10 FM patients [65]. After a 3 week period of vegetarian diet, participants reported an overall improvement in subjective well-being. Some years later, Kaartinen et al. tested a 3 month strict raw vegan diet on 18 FM patients, highlighting a significant improvement in pain scores, joint stiffness and sleep quality [67]. Interestingly, these beneficial effects tended to disappear immediately after shifting back to the omnivorous diet. Similar results with a raw vegan diet were obtained by Hänninen et al. on a group of 33 FM patients after a 3 month intervention period [68] and by Donaldson and colleagues on a sample of 30 FM subjects followed for 7 months [69]. On the other hand, after 6 weeks of dietary intervention with a vegetarian diet, 37 FM patients reported a significant improvement in pain symptoms, but this turned out to be smaller than in a control group of patients receiving a pharmacological treatment with amitriptyline [66]. Finally, a 4 week intervention program combining core stabilization exercises plus a lacto-vegetarian diet in 21 patients with FM who had low back pain led to pain reduction and improved body composition [70].

3.8. Mediterranean Diet

Only little evidence is available on the possible beneficial effects of the Mediterranean diet on FM. A recent cross-sectional study of 95 FM women showed that adherence to the Mediterranean diet was consistently associated with quantitative calcaneal ultrasound parameters, supporting the hypothesis that adherence to the Mediterranean diet may play a determining role in bone health in FM women [82]. Given that alterations in the intestinal bacterial flora appear to be a contributing factor in many chronic inflammatory and degenerative diseases, including rheumatic diseases such as FM, Michalsen and colleagues have tested the effect on the gut microbiota of interventions with the Mediterranean diet or a modified intermittent 8 day fasting regimen in 35 patients affected by FM [71]. Surprisingly, after 2 weeks and 3 months of follow-up, the authors found no significant changes in fecal bacteria counts following the two dietary interventions within and between groups. In addition, no significant differences appeared in the analysis of secretory immunoglobulin A or the symptomatology, suggesting that neither Mediterranean diet nor fasting treatments influenced the gut microbiota or symptoms in FM patients [71]. On the other hand, a recent study of 22 FM patients revealed that a 16 week Mediterranean diet with or without high doses of tryptophan and magnesium led to several beneficial effects on emotional processing, decreased fatigue, anxiety and depression, and reduced possible eating disorders and body image dissatisfaction, with significant greater improvements especially in the Mediterranean diet plus supplements group [72].

4. Conclusions

This review embraced the literature and showed that the role of dietary supplements on FM remains controversial, although clinical trials with vitamin D, magnesium, iron and probiotics’ supplementation show promising results. In terms of dietary interventions, the administration of olive oil, the replacement diet with ancient cereals, low-calorie diets, vegetarian diets, the low-FODMAPs diet, the gluten-free diet, the monosodium glutamate and aspartame-free diet and the Mediterranean diet all appear to be effective in reducing the symptoms of FM. The majority of the included studies showed a significant improvement in chronic pain, anxiety, depression, cognitive function, sleep pattern and gastrointestinal symptoms. In addition, weight loss seems to be associated with both reduced inflammation and improved quality of life in FM subjects, thus suggesting that body weight could have a functional repercussion in these patients. Therefore, the fact that the improvement has been achieved through different dietary strategies may lead to the hypothesis that both weight loss and the psychosomatic component of the disease could have a major role in the disease. In addition, all of these diets are generally regarded as healthy dietary models, rich in plant foods, antioxidants or fiber, so the fact that people have experienced an improvement in symptoms after almost all dietary interventions suggests that an adequate diet could play a crucial role in the management of FM. However, these results should be interpreted with caution since the aforementioned studies present several biases that limit the robustness of the findings. First of all, most studies have a limited sample size with no possibility of blinding due to the nature of dietary intervention trials. Secondly, outcomes are often analyzed using different methodologies and without considering possible confounding factors. In addition, adherence to the assigned dietary intervention is hardly ever evaluated. Finally, a follow-up is almost never carried out to determine whether the positive effects are maintained over time or are only transient. Therefore, although dietary aspects appear to be a promising complementary approach to treat FM, further research is needed to improve the understanding of the disease and to provide the most effective strategies for managing FM syndrome.

Author Contributions

G.P., B.C., I.G. and M.D. wrote the article. F.S. and B.C. participated in the critical revision and final approval. All authors have read and agreed to the published version of the manuscript.


This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.


  1. Clauw, D.J. Fibromyalgia and related conditions. Mayo Clin. Proc. 2015, 90, 680–692. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Gracely, R.H.; Schweinhardt, P. Key mechanisms mediating fibromyalgia. Clin. Exp. Rheumatol. 2015, 33, 3–6. [Google Scholar]
  3. Littlejohn, G.; Guymer, E. Key milestones contributing to the understanding of the mechanisms underlying fibromyalgia. Biomedicines 2020, 8, 223. [Google Scholar] [CrossRef] [PubMed]
  4. Wolfe, F.; Clauw, D.J.; Fitzcharles, M.A.; Goldenberg, D.L.; Hauser, W.; Katz, R.L.; Mease, P.J.; Russell, A.S.; Russell, I.J.; Walitt, B. Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin. Arthritis Rheum. 2016, 46, 319–329. [Google Scholar] [CrossRef]
  5. Clauw, D.J. Fibromyalgia: A clinical review. JAMA 2014, 311, 1547–1555. [Google Scholar] [CrossRef]
  6. Jones, G.T.; Atzeni, F.; Beasley, M.; Flüß, E.; Sarzi-Puttini, P.; Macfarlane, G.J. The prevalence of fibromyalgia in the general population: A comparison of the american college of rheumatology 1990, 2010, and modified 2010 classification criteria. Arthritis Rheumatol. 2015, 65, 568–575. [Google Scholar] [CrossRef] [Green Version]
  7. Borchers, A.T.; Gershwin, M.E. Fibromyalgia: A critical and comprehensive review. Clin. Rev. Allergy Immunol. 2015, 49, 100–151. [Google Scholar] [CrossRef]
  8. Sluka, K.A.; Clauw, D.J. Neurobiology of fibromyalgia and chronic widespread pain. Neuroscience 2016, 338, 114–129. [Google Scholar] [CrossRef]
  9. Ozgocmen, S.; Ozyurt, H.; Sogut, S.; Akyol, O.; Ardicoglu, O.; Yildizhan, H. Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia etiologic and therapeutic concerns. Rheumatol. Int. 2006, 26, 598–603. [Google Scholar] [CrossRef]
  10. García, J.J.; Carvajal-Gil, J.; Herrero-Olea, A.; Gómez-Galán, R. Altered inflammatory mediators in fibromyalgia. Rheumatology 2017, 7, 215–225. [Google Scholar] [CrossRef] [Green Version]
  11. Ablin, J.N.; Cohen, H.; Buskila, D. Mechanisms of disease: Genetics of fibromyalgia. Nat. Clin. Pract. Rheumatol. 2006, 2, 671–678. [Google Scholar] [CrossRef] [PubMed]
  12. Kato, K.; Sullivan, P.F.; Evengard, B.; Pedersen, N.L. Importance of genetic influences on chronic widespread pain. Arthritis Rheum. 2006, 54, 1682–1686. [Google Scholar] [CrossRef] [PubMed]
  13. Docampo, E.; Escaramís, G.; Gratacòs, M.; Villatoro, S.; Puig, A.; Kogevinas, M.; Collado, A.; Carbonell, J.; Rivera, J.; Vidal, J.; et al. Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system. Pain 2014, 155, 1102–1109. [Google Scholar] [CrossRef] [PubMed]
  14. Haviland, M.G.; Morton, K.R.; Oda, K.; Fraser, G.E. Traumatic experiences, major life stressors, and selfreporting a physician-given fibromyalgia diagnosis. Psychiatry Res. 2010, 177, 335–341. [Google Scholar] [CrossRef] [Green Version]
  15. Low, L.A.; Schweinhardt, P. Early life adversity as a risk factor for fibromyalgia in later life. Pain Res. Treat. 2012, 2012, 140832. [Google Scholar] [CrossRef] [Green Version]
  16. D′Agnelli, S.; Arendt-Nielsen, L.; Gerra, M.C.; Zatorri, K.; Boggiani, L.; Baciarello, M.; Bignami, E. Fibromyalgia: Genetics and epigenetics insights may provide the basis for the development of diagnostic biomarkers. Mol. Pain 2019, 15, 1–12. [Google Scholar] [CrossRef]
  17. MacFarlanw, G.J.; Kronish, C.; Dean, L.E.; Atzeni, F.; Häuser, W.; Fluß, E.; Choy, E.; Kosek, E.; Amris, K.; Branco, J.; et al. EULAR revised recommendations for the management of fibromyalgia. Ann. Rheum. Dis. 2017, 76, 318–328. [Google Scholar] [CrossRef]
  18. Aman, M.M.; Yong, R.J.; Kaye, A.D.; Urman, R.D. Evidence-based non-pharmacological therapies for fibromyalgia. Curr. Pain Headache Rep. 2018, 22, 33–37. [Google Scholar] [CrossRef]
  19. Rossi, A.; Di Lollo, A.; Guzzo, M.; Giacomelli, C.; Atzeni, F.; Bazzichi, L.; Di Franco, M. Fibromyalgia and nutrition: What news? Clin. Exp. Rheumatol. 2015, 33 (Suppl. 88), 117–125. [Google Scholar]
  20. Holton, K. The role of diet in the treatment of fibromyalgia. Pain Manag. 2016, 6, 317–320. [Google Scholar] [CrossRef] [Green Version]
  21. Bjørklund, G.; Dadar, M.; Chirumbolo, S.; Aaseth, J. Fibromyalgia and nutrition: Therapeutic possibilities? Biomed. Pharmacother. 2018, 103, 531–538. [Google Scholar] [CrossRef] [PubMed]
  22. Arranz, L.I.; Canela, M.Á.; Rafecas, M. Dietary aspects in fibromyalgia patients: Results of a survey on food awareness, allergies, and nutritional supplementation. Rheumatol. Int. 2012, 32, 2615–2621. [Google Scholar] [CrossRef] [PubMed]
  23. Joustra, M.L.; Minovic, I.; Janssens, K.A.M.; Bakker, S.J.L.; Rosmalen, J.G.M. Vitamin and mineral status in chronic fatigue syndrome and fibromyalgia syndrome: A systematic review and meta-analysis. PLoS ONE 2017, 12, e0176631. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Warner, A.E.; Arnspiger, S.A. Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D. J. Clin. Rheumatol. 2008, 14, 12–16. [Google Scholar] [CrossRef] [PubMed]
  25. Arvold, D.S.; Odean, M.J.; Dornfeld, M.P.; Regal, R.R.; Arvold, J.G.; Karwoski, G.C.; Mast, D.J.; Sanford, P.B.; Sjoberg, R.J. Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: A randomized controlled trial. Endocr. Pract. 2009, 15, 203–212. [Google Scholar] [CrossRef]
  26. Abokrysha, N.T. Vitamin D deficiency in women with fibromyalgia in Saudi Arabia. Pain Med. 2012, 13, 452–458. [Google Scholar] [CrossRef] [Green Version]
  27. Wepner, F.; Scheuer, R.; Schuetz-Wieser, B.; Machacek, P.; Pieler-Bruha, E.; Cross, H.S.; Hahne, J.; Friedrich, M. Effects of vitamin D on patients with fibromyalgia syndrome: A randomized placebo-controlled trial. Pain 2014, 155, 261–268. [Google Scholar] [CrossRef]
  28. Yilmaz, R.; Salli, A.; Cingoz, H.T.; Kucuksen, S.; Ugurlu, H. Efficacy of vitamin D replacement therapy on patients with chronic nonspecific widespread musculoskeletal pain with vitamin D deficiency. Int. J. Rheum. Dis. 2016, 19, 1255–1262. [Google Scholar] [CrossRef] [Green Version]
  29. Dogru, A.; Balkarli, A.; Cobankara, V.; Tunc, S.E.; Sahin, M. Effects of vitamin d therapy on quality of life in patients with fibromyalgia. Eurasian. J. Med. 2017, 49, 113–117. [Google Scholar] [CrossRef]
  30. De Carvalho, J.F.; da Rocha Araújo, F.A.G.; da Mota, L.M.A.; Aires, R.B.; de Araujo, R.P. Vitamin D supplementation seems to improve fibromyalgia symptoms: Preliminary results. Isr. Med. Assoc. J. 2018, 20, 379–381. [Google Scholar]
  31. Mirzaei, A.; Zabihiyeganeh, M.; Jahed, S.A.; Khiabani, E.; Nojomi, M.; Ghaffari, S. Effects of vitamin D optimization on quality of life of patients with fibromyalgia: A randomized controlled trial. Med. J. Islam. Repub. Iran 2018, 32, 29–34. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  32. Naziroglu, M.; Akkus, S.; Soyupek, F.; Yalman, K.; Çelik, O.; Eris, S.; Uslusoy, G.A. Vitamins C and E treatment combined with exercise modulates oxidative stress markers in blood of patients with fibromyalgia: A controlled clinical pilot study. Stress 2010, 13, 498–505. [Google Scholar] [CrossRef] [PubMed]
  33. Russell, I.J.; Michalek, J.E.; Flechas, J.D.; Abraham, G.E. Treatment of fibromyalgia syndrome with super malic: A randomized, double blind, placebo controlled, crossover pilot study. J. Rheumatol. 1995, 22, 953–958. [Google Scholar] [PubMed]
  34. Bagis, S.; Karabiber, M.; As, I.; Tamer, L.; Erdogan, C.; Atalay, A. Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia? Rheumatol. Int. 2013, 33, 167–172. [Google Scholar] [CrossRef]
  35. Boomershine, C.S.; Koch, T.A.; Morris, D. A blinded, randomized, placebo-controlled study to investigate the efficacy and safety of ferric carboxymaltose in iron-deficient patients with fibromyalgia. Rheumatol. Ther. 2018, 5, 271–281. [Google Scholar] [CrossRef] [Green Version]
  36. Roman, P.; Estévez, A.F.; Miras, A.; Sánchez-Labraca, N.; Cañadas, F.; Vivas, A.B.; Cardona, D. A pilot randomized controlled trial to explore cognitive and emotional effects of probiotics in fibromyalgia. Sci. Rep. 2018, 8, 10965. [Google Scholar] [CrossRef]
  37. Al-Allaf, A.; Mole, P.; Paterson, C.; Pullar, T. Bone health in patients with fibromyalgia. Rheumatology 2003, 42, 1202–1206. [Google Scholar] [CrossRef] [Green Version]
  38. Armstrong, D.; Meenagh, G.; Bickle, I.; Lee, A.; Curran, E.S.; Finch, M. Vitamin D deficiency is associated with anxiety and depression in fibromyalgia. Clin. Rheumatol. 2007, 26, 551–554. [Google Scholar] [CrossRef]
  39. Olama, S.M.; Senna, M.K.; Elarman, M.M.; Elhawary, G. Serum vitamin D level and bone mineral density in premenopausal egyptian women with fibromyalgia. Rheumatol. Int. 2013, 33, 185–192. [Google Scholar] [CrossRef]
  40. Ulatowski, L.M.; Manor, D. Vitamin E and neurodegeneration. Neurobiol. Dis. 2015, 84, 78–83. [Google Scholar] [CrossRef]
  41. Engen, D.J.; McAllister, S.J.; Whipple, M.O.; Cha, S.S.; Dion, L.J.; Vincent, A.; Bauer, B.A.; Wahner-Roedler, D.L. Effects of transdermal magnesium chloride on quality of life for patients with fibromyalgia: A feasibility study. J. Integr. Med. 2015, 13, 306–313. [Google Scholar] [CrossRef]
  42. Kasim, A.A. Calcium, magnesium and phosphorous levels in serum of iraqi women with fibromyalgia. Iraqi J. Pharm. Sci. 2017, 20, 34–37. [Google Scholar]
  43. Andretta, A.; Batista, E.D.; Schieferdecker, M.E.M.; Petterle, R.R.; Boguszewski, C.L.; Paiva, E.D.S. Relation between magnesium and calcium and parameters of pain, quality of life and depression in women with fibromyalgia. Adv. Rheumatol. 2019, 59, 55–60. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. Porter, N.S.; Jason, L.A.; Boulton, A.; Bothne, N.; Coleman, B. Alternative medical interventions used in the treatment and management of myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia. J. Altern. Complement. Med. 2010, 16, 235–249. [Google Scholar] [CrossRef] [PubMed]
  45. Pamuk, G.E.; Pamuk, O.N.; Set, T.; Harmandar, O.; Yeşil, N. An increased prevalence of fibromyalgia in iron deficiency anemia and thalassemia minor and associated factors. Clin. Rheumatol. 2008, 27, 1103–1108. [Google Scholar] [CrossRef]
  46. Ortancil, O.; Sanli, A.; Eryuksel, R.; Basaran, A.; Ankarali, H. Association between serum ferritin level and fibromyalgia syndrome. Eur. J. Clin. Nutr. 2010, 64, 308–312. [Google Scholar] [CrossRef]
  47. Kim, Y.S.; Kim, K.M.; Lee, D.J.; Kim, B.T.; Park, S.B.; Cho, D.Y.; Suh, C.H.; Kim, H.A.; Park, R.W.; Joo, N.S. Women with fibromyalgia have lower levels of calcium, magnesium, iron and manganese in hair mineral analysis. J. Korean Med. Sci. 2011, 26, 1253–1257. [Google Scholar] [CrossRef]
  48. Minerbi, A.; Fitzcharles, M.A. Gut microbiome: Pertinence in fibromyalgia. Clin. Exp. Rheumatol. 2020, 38 (Suppl. 123), 99–104. [Google Scholar]
  49. Bazzichi, L.; Palego, L.; Giannaccini, G.; Rossi, A.; De Feo, F.; Giacomelli, C.; Betti, L.; Giusti, L.; Mascia, G.; Bombardieri, S.; et al. Altered amino acid homeostasis in subjects affected by fibromyalgia. Clin. Biochem. 2009, 42, 1064–1070. [Google Scholar] [CrossRef]
  50. Schwarz, M.J.; Offenbaecher, M.; Neumeister, A.; Ackenheil, M. Experimental evaluation of an altered tryptophan metabolism in fibromyalgia. Adv. Exp. Med. Biol. 2003, 527, 265–275. [Google Scholar]
  51. Rus, A.; Molina, F.; Ramos, M.M.; Martínez-Ramírez, M.J.; Del Moral, M.L. Extra virgin olive oil improves oxidative stress, functional capacity, and health-related psychological status in patients with fibromyalgia: A preliminary study. Biol. Res. Nurs. 2017, 19, 106–115. [Google Scholar] [CrossRef] [PubMed]
  52. Rus, A.; Molina, F.; Martínez-Ramírez, M.J.; Aguilar-Ferrándiz, M.E.; Carmona, R.; Del Moral, M.L. Effects of olive oil consumption on cardiovascular risk factors in patients with fibromyalgia. Nutrients 2020, 12, 918. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  53. Pagliai, G.; Colombini, B.; Dinu, M.; Whittaker, A.; Masoni, A.; Danza, G.; Amedei, A.; Ballerini, G.; Benedettelli, S.; Sofi, F. Effectiveness of a Khorasan wheat-based replacement on pain symptoms and quality of life in patients with fibromyalgia. Pain Med. 2020. [Google Scholar] [CrossRef] [PubMed]
  54. Holton, K.F.; Taren, D.L.; Thomson, C.A.; Bennett, R.M.; Jones, K.D. The effect of dietary glutamate on fibromyalgia and irritable bowel symptoms. Clin. Exp. Rheumatol. 2012, 30 (Suppl. 74), 10–17. [Google Scholar] [PubMed]
  55. Vellisca, M.Y.; Latorre, J.I. Monosodium glutamate and aspartame in perceived pain in fibromyalgia. Rheumatol. Int. 2014, 34, 1011–1013. [Google Scholar] [CrossRef]
  56. Rodrigo, L.; Blanco, I.; Bobes, J.; de Serres, F.J. Clinical impact of a gluten-free diet on health-related quality of life in seven fibromyalgia syndrome patients with associated celiac disease. BMC Gastroenterol. 2013, 13, 157. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  57. Rodrigo, L.; Blanco, I.; Bobes, J.; de Serres, F.J. Effect of one year of a gluten-free diet on the clinical evolution of irritable bowel syndrome plus fibromyalgia in patients with associated lymphocytic enteritis: A case-control study. Arthritis Res. Ther. 2014, 16, 421–431. [Google Scholar]
  58. Isasi, C.; Colmenero, I.; Casco, F.; Tejerina, E.; Fernandez, N.; Serrano-Vela, J.I.; Castro, M.J.; Villa, L.F. Fibromyalgia and non-celiac gluten sensitivity: A description with remission of fibromyalgia. Rheumatol. Int. 2014, 34, 1607–1612. [Google Scholar] [CrossRef] [Green Version]
  59. Slim, M.; Calandre, E.P.; Garcia-Leiva, J.M.; Rico-Villademoros, F.; Molina-Barea, R.; Rodriguez-Lopez, C.M.; Morillas-Arques, P. The effects of a gluten-free diet versus a hypocaloric diet among patients with fibromyalgia experiencing gluten sensitivity-like symptoms: A pilot, open-label randomized clinical trial. J. Clin. Gastroenterol. 2017, 51, 500–507. [Google Scholar] [CrossRef]
  60. Marum, A.P.; Moreira, C.; Saraiva, F.; Tomas-Carus, P.; Sousa-Guerreiro, C. A low fermentable oligo-di-mono saccharides and polyols (FODMAP) diet reduced pain and improved daily life in fibromyalgia patients. Scand. J. Pain 2016, 13, 166–172. [Google Scholar] [CrossRef]
  61. Marum, A.P.; Moreira, C.; Tomas-Carus, P.; Saraiva, F.; Guerreiro, C.S. A low fermentable oligo-di-mono-saccharides and polyols (FODMAP)diet is a balanced therapy for fibromyalgia with nutritional and symptomatic benefits. Nutr. Hosp. 2017, 34, 667–674. [Google Scholar] [CrossRef] [PubMed]
  62. Shapiro, J.R.; Anderson, D.A.; Danoff-Burg, S. A pilot study of the effects of behavioral weight loss treatment on fibromyalgia symptoms. J. Psychosom. Res. 2005, 59, 275–282. [Google Scholar] [CrossRef] [PubMed]
  63. Senna, M.K.; Sallam, R.A.; Ashour, H.S.; Elarman, M. Effect of weight reduction on the quality of life in obese patients with fibromyalgia syndrome: A randomized controlled trial. Clin. Rheumatol. 2012, 31, 1591–1597. [Google Scholar] [CrossRef] [PubMed]
  64. Schrepf, A.; Harte, S.E.; Miller, N.; Fowler, C.; Nay, C.; Williams, D.A.; Clauw, D.J.; Rothberg, A. Improvement in the spatial distribution of pain, somatic symptoms, and depression following a weight-loss intervention. J. Pain 2017, 18, 1542–1550. [Google Scholar] [CrossRef]
  65. Hostmark, A.T.; Lystad, E.; Vellar, O.D.; Hovi, K.; Berg, J.E. Reduced plasma fibrinogen, serum peroxides, lipids, and apolipoproteins after a 3-week vegetarian diet. Plant Foods Hum. Nutr. 1993, 43, 55–61. [Google Scholar] [CrossRef]
  66. Azad, K.A.; Alam, M.N.; Haq, S.A.; Nahar, S.; Chowdhury, M.A.; Ali, S.M.; Ullah, A.K. Vegetarian diet in the treatment of fibromyalgia. Bangladesh Med. Res. Counc. Bull. 2000, 26, 41–47. [Google Scholar]
  67. Kaartinen, K.; Lammi, K.; Hypen, M.; Nenonen, M.; Hanninen, O.; Rauma, A.L. Vegan diet alleviates fibromyalgia symptoms. Scand. J. Rheumatol. 2000, 29, 308–313. [Google Scholar] [CrossRef]
  68. Hänninen, O.; Kaartinen, K.; Rauma, A.L.; Nenonen, M.; Törrönen, R.; Häkkinen, A.S.; Adlercreutz, H.; Laakso, J. Antioxidants in vegan diet and rheumatic disorders. Toxicology 2000, 155, 45–53. [Google Scholar] [CrossRef]
  69. Donaldson, M.S.; Speight, N.; Loomis, S. Fibromyalgia syndrome improved using a mostly raw vegetarian diet: An observational study. BMC Complement. Altern. Med. 2001, 1, 7. [Google Scholar] [CrossRef] [Green Version]
  70. Martínez-Rodríguez, A.; Leyva-Vela, B.; Martínez-García, A.; Nadal-Nicolás, Y. Efectos de la dieta lacto-vegetariana y ejercicios de estabilización del core sobre la composición corporal y el dolor en mujeres con fibromialgia: Ensayo controlado aleatorizado [Effects of lacto-vegetarian diet and stabilization core exercises on body composition and pain in women with fibromyalgia: Randomized controlled trial]. Nutr. Hosp. 2018, 35, 392–399. [Google Scholar]
  71. Michalsen, A.; Riegert, M.; Lüdtke, R.; Bäcker, M.; Langhorst, J.; Schwickert, M.; Dobos, G.J. Mediterranean diet or extended fasting’s influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: An observational study. BMC Complement. Altern. Med. 2005, 5, 22. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  72. Martínez-Rodríguez, A.; Rubio-Arias, J.Á.; Ramos-Campo, D.J.; Reche-García, C.; Leyva-Vela, B.; Nadal-Nicolás, Y. Psychological and sleep effects of tryptophan and magnesium-enriched mediterranean diet in women with fibromyalgia. Int. J. Environ. Res. Public Health 2020, 17, 2227. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  73. Whittaker, A.; Dinu, M.; Cesari, F.; Gori, A.M.; Fiorillo, C.; Becatti, M.; Casini, A.; Marcucci, R.; Benedettelli, S.; Sofi, F. A Khorasan wheat-based replacement diet improves risk profile of patients with type 2 diabetes mellitus (T2DM): A randomized crossover trial. Eur. J. Nutr. 2017, 56, 1191–1200. [Google Scholar] [CrossRef] [Green Version]
  74. Dinu, M.; Whittaker, A.; Pagliai, G.; Giangrandi, I.; Colombini, B.; Gori, A.M.; Fiorillo, C.; Becatti, M.; Casini, A.; Benedettelli, S.; et al. A Khorasan wheat-based replacement diet improves risk profile of patients with nonalcoholic fatty liver disease (NAFLD): A randomized clinical trial. J. Am. Coll. Nutr. 2018, 37, 508–514. [Google Scholar] [CrossRef] [Green Version]
  75. Sofi, F.; Whittaker, A.; Cesari, F.; Gori, A.M.; Fiorillo, C.; Becatti, M.; Marotti, I.; Dinelli, G.; Casini, A.; Abbate, R.; et al. Characterization of Khorasan wheat (Kamut) and impact of a replacement diet on cardiovascular risk factors: Cross-over dietary intervention study. Eur. J. Clin. Nutr. 2013, 67, 190–195. [Google Scholar] [CrossRef] [Green Version]
  76. Smith, J.D.; Terpening, C.M.; Schmidt, S.O.; Gums, J.G. Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins. Ann. Pharmacother. 2001, 35, 702–706. [Google Scholar] [CrossRef] [PubMed]
  77. Ciappuccini, R.; Ansemant, T.; Maillefert, J.F.; Tavernier, C.; Ornetti, P. Aspartame-induced fibromyalgia, an unusual but curable cause of chronic pain. Clin. Exp. Rheumatol. 2010, 28 (Suppl. 63), S131–S133. [Google Scholar] [PubMed]
  78. Orlando, A.; Tutino, V.; Notarnicola, M.; Riezzo, G.; Linsalata, M.; Clemente, C.; Prospero, L.; Martulli, M.; D′Attoma, B.; De Nunzio, V.; et al. Improved symptom profiles and minimal inflammation in IBS-D patients undergoing a long-term low-FODMAP diet: A lipidomic perspective. Nutrients 2020, 12, 1652. [Google Scholar] [CrossRef]
  79. Helfenstein, M.; Heymann, R.; Feldman, D. Prevalence of irritable bowel syndrome in patients with fibromyalgia. Rev. Bras. Reum. 2006, 46, 16–23. [Google Scholar]
  80. Arranz, L.I.; Canela, M.A.; Rafecas, M. Fibromyalgia and nutrition, what do we know? Rheumatol. Int. 2010, 30, 1417–1427. [Google Scholar] [CrossRef] [Green Version]
  81. Steck, S.; Shivappa, N.; Tabung, F.; Harmon, B.; Wirth, M.; Hurley, T.; Hebert, J. The dietary inflammatory index: A new tool for assessing diet quality based on inflammatory potential. Digest 2014, 49, 1–10. [Google Scholar]
  82. Correa-Rodríguez, M.; El Mansouri-Yachou, J.; Tapia-Haro, R.M.; Molina, F.; Rus, A.; Rueda-Medin, A.B.; Aguilar-Ferrandiz, M.E. Mediterranean diet, body composition, and activity associated with bone health in women with fibromyalgia syndrome. Nurs. Res. 2019, 68, 358–364. [Google Scholar] [CrossRef] [PubMed]
Table 1. Nutritional supplementation in fibromyalgia (FM) subjects.
Table 1. Nutritional supplementation in fibromyalgia (FM) subjects.
Author, YearCountryIntervention, nControl, nAge, ySexDurationInterventionControlOutcomesFindingsEfficacy *
Vitamin D
Warner et al., 2008 [24]US252558.0 ± 7.3 intervention; 56.7 ± 11.3 controlF12 weeks50,000 IU of oral ergocalciferol weeklyPlacebo25(OH)D, duration of pain, VAS, FPS25(OH)D increase in the intervention group; no difference in duration of pain, VAS and FPS score=
Arvold et al., 2009 [25]US484259.7 ± 14.0 intervention; 57.8 ± 15.8 controlAll8 weeks50,000 IU of oral cholecalciferol weeklyPlacebo25(OH)D, PTH, creatinine, calcium, self-reported symptoms, FIQ25(OH)D increase and PTH decrease in the intervention group. 5 out 20 FIQ items and total FIQ score improved after intervention. Severely deficient patients did not show symptom improvement+
Abokrysha et al., 2012 [26]Saudi Arabia30NA34.6 ± 8.1F8 weeks600,000 IU of intramuscular single dose or 50,000 IU oral cholecalciferol weeklyNAWPI, fatigue, waking unrefreshed, cognition, SSImprovement of WPI, fatigue, waking unrefreshed and SS score after treatment+
Wepner et al., 2014 [27]Austria151548.4 ± 5.3All20 weeks2400 IU or 1200 IU (according to serum calcifediol levels) of cholecalciferol dailyPlaceboCalcifediol, pain severity (VAS), SF-36; HADS-D, FIQ, SCL-90-RSeverity of pain and physical role functioning scale improved after intervention +/=
Yilmaz et al., 2016 [28]Turkey30NA36.9 ± 9.2All12 weeks50,000 IU of oral cholecalciferol weeklyNACa, P, ALP, 25(OH) D, pain severity (VAS), asthenia (VAS), TPC, BDI, SF-36, waking unrefreshed, headache, tenderness on tibiaMarked decrease in pain, asthenia, severity of waking unrefreshed, TPC, and BDI and improvement in quality of life after treatment+
Dogru et al., 2017 [29]Turkey422838.7 ± 5.2F12 weeks50,000 IU of oral cholecalciferol weeklyNo treatmentFIQ, SF-36, pain severity (VAS), ASEX, BDIImprovements in physical function, physical role limitations, emotional role limitations, social function, mental health, vitality, and quality of life after treatment+
de Carvalho et al., 2018 [30]Brazil11NA48.5 (28-67)F12 weeks50,000 IU of oral cholecalciferol weeklyNA25(OH)D, pain severity (VAS), TPCImprovements in 25(OH)D levels, pain severity and reduction in TPC+
Mirzaei et al., 2018 [31]Iran373742.1 ± 10.8 intervention;
41.0 ± 10.3 control
All8 weeksTrazodone 25 mg + 50,000 IU of oral cholecalciferol weeklyTrazodone 25 mg + placebo25(OH)D, WPI, FIQ, PSQI, SF-36Improvement in 25(OH)D, WPI, FIQ, PSQI and SF-36 in the intervention group+
Vitamin C + E
Naziroglu et al., 2010 [32]Turkey21
(n = 11 vit. C + E; n = 10) vit. C+E + exercise)
1140.5 ± 4.9 vit. C + E; 37.4 ± 4.0 vit. C + E + exercise;
37.8 ± 8.7 control
F12 weeks150 mg/day of α
-tocopheryl acetate and 500 mg/day ascorbic acid or 150 mg/day of α
-tocopheryl acetate and 500 mg/day ascorbic acid + exercise
ExerciseVitamin A, C and E, β-carotene, LP, GSH, GSH-Px, pain severity (VAS)Improvement of LP, GSH, GSH- Px and plasma vitamins A, C, and E after the supplementations with or without exercise+/=
Russell et al., 1995 [33]US121249F4 weeks200 mg malic acid + 50 mg magnesium, 3 tablets/day up to 6 tablets/dayPlaceboPain severity (VAS), TPC, TPA, HAQ, CESD, Hassle, psychological response to eventsLittle or no effect with low doses; improvements in the severity of primary pain/tenderness measures with dose escalation and a longer duration of treatment +/=
Bagis et al., 2013 [34]Turkey40
(n = 20 Mg citrate; n = 20 Mg citrate + amitriptyline)
2040.2 ± 5.1
Mg citrate;40.7 ± 5.2
Mg citrate + amitriptyline; 42.1 ± 6.2
F8 weeks300 mg/day of Mg citrate or 300 mg/day of Mg citrate + 10 mg/day amitriptyline 10 mg/day amitriptylinePain severity (VAS), TPC, FIQ, BDI, BAI, self-reported symptomsImprovement in TPC, FIQ and BDI with the Mg citrate treatment.
Improvement in almost all parameters except for pain, FIQ, headache, gastric problems, IBS, cramps after amitriptyline treatment.
Improvement in all parameters except numbness after the combined amitriptyline + Mg citrate treatment
Boomershine et al., 2018 [35]US414041.2 ± 11.1 intervention;
43.9 ± 10.8 control
All6 weeks15 mg/kg (up to 750 mg) of ferric carboxymaltose for 5 daysPlaceboIron indices, hematology parameters, FIQR, BPI, MOS Sleep scale, Fatigue VNSImprovement in FIQ, BPI, fatigue and iron indices in the treatment group.+
Roman et al., 2018 [36]Spain202055.0 ± 8.4 intervention;
50.3 ± 7.9 control
All7 weeks4 pills/day containing Lactobacillus Rhamnosus GG®, Casei, Acidophilus, and Bifidobacterium BifidusPlaceboPain severity (VAS), FIQ, SF-36, BDI, STAI, MMSE, cortisolImproved impulsivity and decision-making after the intervention+/=
ALP—alkaline phosphatase; ASEX—Arizona sexual life questionnaire; BAI—Beck Anxiety Inventory; BDI—Beck Depression Inventory; BPI—Brief Pain Inventory; CESD—Center for Epidemiologic Studies Depression Scale score; FIQ—Fibromyalgia Impact Questionnaire; FIQR—Revised Fibromyalgia Impact Questionnaire; FPS—Functional Pain Score; GSH—glutathione; GSH-Px—glutathione peroxidase; HADS-D—Hospital Anxiety Depression Scale Deutsche version; HAQ—Health Assessment Questionnaire; Hassle—Hassle Scale score; LP—lipid peroxidation; MMSE—Mini Mental State Examination; MOS—Medical Outcomes Study Sleep Scale; NA—Not applicable; PSQI—Pittsburgh Sleep Quality Index; PTH—parathyroid hormone; SCL-90-R—Symptom Checklist-90-Revised; SF-36—Short Form Health Survey; SS—Symptom severity score; STAI—State Trait Anxiety Inventory; TPA—tender point average; TPC—tender point count; VAS—Visual Analogue Scale; VNS—Visual Numeric Scale; WPI—Widespread Pain Index. * + significant improvement in (almost) all the investigated outcomes; = no significant improvement in the investigated outcomes.
Table 2. Dietary interventions in FM subjects.
Table 2. Dietary interventions in FM subjects.
Author, YearCountryIntervention, nControl, nAge, ySexDurationInterventionControlOutcomesFindingsEfficacy *
Olive oil
Rus et al., 2017 [51]Spain111253.6 ± 5.5 intervention; 48.2 ± 8.0 controlF3 weeks50 mL/die EVOO50 mL/die ROOBMI, SBP, DBP, cardiac frequency, oxidative stress markers, antioxidative markers, FIQ, pain severity (VAS), PCS-12, MCS-12Improvement in protein carbonyls, lipid peroxidation, FIQ and mental health status after the intervention with EVOO+
Rus et al., 2020 [52]Spain 151554.1 ± 5.6
49.8 ± 5.8 control
F3 weeks50 mL/die EVOO50 mL/die ROOweight, BMI, waist circumference, thrombosis-related parameters, ESR, inflammatory markers, NO, lipid profile, cortisolEVOO declined red blood cell count and ESR. ROO increased mean platelet volume and reduced PDW, neutrophil-to-lymphocyte ratio, ESR and fibrinogen. Significant differences in pre–post change between EVOO and ROO for cortisol and PDW+
Ancient grain
Pagliai et al., 2020 [53]Italy101046.2 ± 11.5 intervention; 51.7 ± 12.9 controlAll8 weeksPasta, bread, cracker, biscuits made with ancient grain KhorasanPasta, bread, cracker, biscuits made with modern grain PalesioWPI, SS, FIQ, FSS, TSS, SRSBQ, RSQD, FOSQImprovement in WPI + SS, FIQ and FOSQ after the intervention+
MSG and aspartame-free diet
Holton et al., 2012 [54]US46NA53.0 ± 13.0All4 weeksMSG and aspartame-free dietNA28-symptom checklist, pain severity (VAS), FIQR, IBS QOLImprovement in all the tested outcomes after the intervention+
Vellisca et al., 2014 [55]Spain363642.3 ± 8.4 intervention;
39.6 ± 8.2
F12 weeksMSG and aspartame-free dietFree dietPain severity (VAS)No significant differences in pain referred after the intervention=
Gluten-free diet
Rodrigo et al., 2013 [56]Spain7NA49.0 ± 12.0F1 yearGluten-free dietNATPC, FIQ, HAQ, SF-36, gastrointestinal complaints (VAS), pain severity (VAS), fatigue (VAS), tTGImprovement of all the tested outcomes after the intervention+
Rodrigo et al., 2014 [57]Spain97NA50.0 ± 8.0All1 yearGluten-free dietNATPC, FIQ, HAQ, SF-36, gastrointestinal complaints (VAS), pain severity (VAS), fatigue (VAS)Improvement of all the tested outcomes after the intervention only in the lymphocytic enteritis subgroup+
Isasi et al., 2014 [58]Spain20NA46 (25–73)F16 monthsGluten-free dietNAWidespread pain, return to work, return to normal lifeImprovement of all the tested outcomes after the intervention+
Slim et al., 2017 [59]Spain354052 (36–66) intervention; 53 (32–65) controlF24 weeksGluten-free dietHypocaloric dietNCGS symptoms, BMI, waist circumference, FIQR, PSQI, BPI-SF, BDI, STAI, SF-12, PGI-SNo statistically significant difference in the tested outcomes between intervention and control treatment=
Low-FODMAPs diet
Marum et al., 2016 [60]Portugal38NA38.5 ± 10.0F4 weeksLow-FODMAPs dietNAFSQ, FIQR, IBS-SSS, EQ-5D, abdominal and somatic pain (VAS), satisfactionImprovements in VAS, FSQ, FIQR and GI symptom+
Marum et al., 2017 [61]Portugal38NA38.5 ± 10.0F4 weeksLow-FODMAPs dietNABody weight, BMI, body composition, waist circumferenceWeight, BMI and waist circumference decreased after the intervention, but no significant effect on body composition+
Low-calorie diet
Shapiro et al., 2005 [62]US42NA54.5 ± 8.1F5 monthsHypocaloric diet (1200–1500 kcal/die)NABody weight, BMI, waist circumference, FIQ, HAQ, MPI, BDI-II, STAI, QOL, BSQImprovement in pain, body image, anxiety, quality of life and depression after the intervention+
Senna et al., 2012 [63]Egypt434344.8 ± 13.6 intervention; 46.3 ± 14.4 controlAll6 monthsHypocaloric diet (1200 kcal/die: 50% CHO, 30% Fat, 20% Protein)Isocaloric dietFIQ, TPC, BDI-II, PSQI, Body weight, BMI, waist circumference, IL-6, CRPImprovements in pain, fatigue, depression, IL-6, CRP+
Schrepf et al., 2017 [64]US123NA50.7 (23–69)All12 weeksHypocaloric diet (800 kcal/die)NABody weight, WPI, SS IDS, inflammatory markersImprovements in pain, symptom severity, depression, FM scores, IL-10 after weight loss+
Vegetarian diet
Hostmark et al., 1993 [65]Norway10NA49.9 ± 4.1All3 weeksVegetarian dietNAPeroxides, lipid profile, apolipoproteins, fibrinogenImprovements in serum peroxide concentration, fibrinogen, total cholesterol, apolipoprotein-B and -A+
Azad et al., 2000 [66]Bangladesh3741NAAll6 weeksVegetarian dietAmitriptylineFatigue, insomnia, non-restorative sleep, pain severity (VAS), TPCNo statistically significant difference in the tested outcomes between intervention and control treatment=
Kaartinen et al., 2000 [67]Finland181551 (34–62) intervention;
52 (37–59) control
F12 weeksRaw vegan dietOmnivorous dietBMI, HAQ, TPC, pain severity (VAS), BDI, sleep, haematocrit, ESR, total cholesterol, urinary Na, GHQ, physical activityImprovements in pain, autonomy, sleep quality, morning stiffness, total cholesterol and urinary Na after the intervention+
Hänninen et al., 2000 [68]Finland3320NA 12 weeksRaw vegan dietOmnivorous dietAntioxidants, lignan, carotenoids, vitamins, morning stiffness, pain severity (VAS)Improvements of carotenoids, phenolic compounds, vitamin C and E, joint stiffness, pain, general well-being after the intervention+
Donaldson et al., 2001 [69]US30NANAAll7 monthsRaw vegan dietNAFIQ, SF-36, QOL, physical performanceImprovement in pain, vitality, mobility, general well-being after the intervention+
Martínez-Rodríguez et al., 2018 [70]Spain14
(n = 7 LOV; n = 7 LOV + exercise)
734.0 ± 2.0 LOV + exercise;
34.0 ± 2.0 LOV;
33.0 ± 3.0 control
F4 weeksLOV or LOV + exerciseFree diet and no exercisePain severity (VAS), body compositionImprovement in body composition and pain severity after the intervention with diet and exercise+
Mediterranean diet
Michalsen et al., 2005 [71]Germany142151.6 ± 13.3 intervention; 52.0 ± 10.0
All8 weeksMediterranean diet8-days fastingGut microbiota composition, stool pH, IgA, pain severity (VAS)No statistically significant difference in the tested outcomes between intervention and control treatment=
Martínez-Rodríguez et al., 2020 [72]Spain111148.0 ± 4.0 intervention; 50.0 ± 5.0
F16 weeksMediterranean diet + 60 mg of tryptophan and 60 mg of MgMediterranean dietPSQI, BSQ, STAI, POMS-29, EAT-26Improvements in anxiety, mood disturbance, eating disorders, dissatisfaction with body image after tryptophan and Mg-enriched Mediterranean diet+
BDI—Beck Depression Inventory; BPI-SF—Brief Pain Inventory-short form; BMI—Body Mass Index; BSQ—Body Shape Questionnaire; CRP—C-reactive protein; DBP—Diastolic blood pressure; EAT-26—Eating Attitude Test-26; EQ-5D—Euro-QOL quality of life instrument; ESR—erythrocyte sedimentation rate; EVOO—Extra-virgin olive oil; FIQ—Fibromyalgia Impact Questionnaire; FSQ—Fibromyalgia Survey Questionnaire; FSS—Fatigue Severity Scale; GHQ—General Health Questionnaire; HAQ—Stanford Health Assessment Questionnaire; IBS QOL—Inflammatory Bowel Disease Quality of Life; IBS-SSS—Irritable Bowel Syndrome-Symptom Severity Survey; IDS—Inventory of Depressive Symptomology; IL—Interleukin; LOV—Lacto-ovo-vegetarian diet MCS-12—Mental Component Summary of the Short Form-12 Health Survey; MPI—West Haven-Yale Multidimensional Pain Inventory; MSG—Monosodium-glutamate; PSC-12—Physical Component Summary of the Short Form-12 Health Survey; NA—Not applicable; NCGS—Non-celiac gluten sensitivity; PDW—platelet distribution width; PGI-S—Patient Global Impression scales of severity; POMS-29—Profile of Mood States Questionnaire; PSQI—Pittsburgh Sleep Quality index; QOL—Quality Of Life Survey; ROO—Refined olive oil; RSQD—Restorative Sleep Questionnaire–Daily; SBP—Systolic blood pressure; SF-12—Short Form Health Survey; SF-36—Short Form Health Survey; SRSBQ—Sleep-Related and Safety Behaviour Questionnaire; SS—Symptom Severity scale; STAI: State Trait Anxiety Inventory; TPC—tender point count; TSS—Tiredness Symptoms Scale; tTG—tissue-Trans-Glutaminase; VAS—Visual analogue scale; WPI—Widespread Pain Index. * + significant improvement in (almost) all the investigated outcomes; = no significant improvement in the investigated outcomes.

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Pagliai, G.; Giangrandi, I.; Dinu, M.; Sofi, F.; Colombini, B. Nutritional Interventions in the Management of Fibromyalgia Syndrome. Nutrients 2020, 12, 2525.

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Pagliai G, Giangrandi I, Dinu M, Sofi F, Colombini B. Nutritional Interventions in the Management of Fibromyalgia Syndrome. Nutrients. 2020; 12(9):2525.

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Pagliai, Giuditta, Ilaria Giangrandi, Monica Dinu, Francesco Sofi, and Barbara Colombini. 2020. "Nutritional Interventions in the Management of Fibromyalgia Syndrome" Nutrients 12, no. 9: 2525.

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