Low-carbohydrate and ketogenic diets: a scoping review of neurological and inflammatory outcomes in human studies and their relevance to chronic pain.

Dietary restriction of carbohydrate has been demonstrated to be beneficial for nervous system dysfunction in animal models and may be beneficial for human chronic pain. The purpose of this review is to assess the impact of a low-carbohydrate/ketogenic diet on the adult nervous system function and inflammatory biomarkers to inform nutritional research for chronic pain. An electronic database search was carried out in May 2021. Publications were screened for prospective research with dietary carbohydrate intake <130 g per day and duration of ≥2 weeks. Studies were categorised into those reporting adult neurological outcomes to be extracted for analysis and those reporting other adult research outcomes. Both groups were screened again for reported inflammatory biomarkers. From 1548 studies, there were 847 studies included. Sixty-four reported neurological outcomes with 83% showing improvement. Five hundred and twenty-three studies had a different research focus (metabolic n = 394, sport/performance n = 51, cancer n = 33, general n = 30, neurological with non-neuro outcomes n = 12, or gastrointestinal n = 4). The second screen identified sixty-three studies reporting on inflammatory biomarkers, with 71% reporting a reduction in inflammation. The overall results suggest a favourable outcome on the nervous system and inflammatory biomarkers from a reduction in dietary carbohydrates. Both nervous system sensitisation and inflammation occur in chronic pain, and the results from this review indicate it may be improved by low-carbohydrate nutritional therapy. More clinical trials within this population are required to build on the few human trials that have been done.

Effects of a Low-Carbohydrate Ketogenic Diet on Reported Pain, Blood Biomarkers and Quality of Life in Patients with Chronic Pain: A Pilot Randomized Clinical Trial.

BACKGROUND: A low-carbohydrate ketogenic diet has been reported to improve chronic pain by reducing inflammation, oxidative stress, and sensitivity within the nervous system. The main aim of this trial is to evaluate the effects of a ketogenic diet on reported pain, blood biomarkers and quality of life in patients with chronic pain. METHODS: Participants with chronic musculoskeletal pain were recruited for a 12-week diet intervention that commenced with a 3-week run-in diet removing ultra-processed foods, followed by randomization to either a whole-food/well-formulated ketogenic diet (WFKD) or to continue with the minimally processed whole-food diet (WFD). Outcome measures included: average pain (visual analogue scale VAS), blood biomarkers, anthropometrics, adherence, depression, anxiety, sleep, ketones, quality of life, diet satisfaction, and macronutrient intake. RESULTS: Average weekly pain improved for both groups. WFKD group VAS reduced by 17.9 ± 5.2 mm (P = .004) and the WFD group VAS reduced 11.0 ± 9.0 mm (P = .006). Both groups also reported improved quality of life (WFKD = 11.5 ± 2.8%, P = .001 and WFD = 11.0 ± 3.5%, P = .014). The WFKD group also demonstrated significant improvements in pain interference (P = 0.013), weight (P < .005), depression (P = .015), anxiety (P = .013), and inflammation (hsCRP) (P = .009). Significant average pain reduction remained at three-month follow-up for both groups (WFKD P = .031, WFD P = .011). CONCLUSIONS: The implementation of a whole-food diet that restricts ultra-processed foods is a valid pain management tool; however, a low-carbohydrate ketogenic diets may have potentially greater pain reduction, weight loss and mood improvements.

Ketogenic diets and the nervous system: a scoping review of neurological outcomes from nutritional ketosis in animal studies.

OBJECTIVES: Ketogenic diets have reported efficacy for neurological dysfunctions; however, there are limited published human clinical trials elucidating the mechanisms by which nutritional ketosis produces therapeutic effects. The purpose of this present study was to investigate animal models that report variations in nervous system function by changing from a standard animal diet to a ketogenic diet, synthesise these into broad themes, and compare these with mechanisms reported as targets in pain neuroscience to inform human chronic pain trials. METHODS: An electronic search of seven databases was conducted in July 2020. Two independent reviewers screened studies for eligibility, and descriptive outcomes relating to nervous system function were extracted for a thematic analysis, then synthesised into broad themes. RESULTS: In total, 170 studies from eighteen different disease models were identified and grouped into fourteen broad themes: alterations in cellular energetics and metabolism, biochemical, cortical excitability, epigenetic regulation, mitochondrial function, neuroinflammation, neuroplasticity, neuroprotection, neurotransmitter function, nociception, redox balance, signalling pathways, synaptic transmission and vascular supply. DISCUSSION: The mechanisms presented centred around the reduction of inflammation and oxidative stress as well as a reduction in nervous system excitability. Given the multiple potential mechanisms presented, it is likely that many of these are involved synergistically and undergo adaptive processes within the human body, and controlled animal models that limit the investigation to a particular pathway in isolation may reach differing conclusions. Attention is required when translating this information to human chronic pain populations owing to the limitations outlined from the animal research.

Experience of participants with chronic pain in a pilot randomized clinical trial using a ketogenic diet.

Aim: To report the experience of chronic pain participants after a well-formulated ketogenic diet (WFKD) or whole-food diet (WFD). The quantitative outcomes for this trial have been published separately (clinical trial registration number ACTRN12620000946910). Patients & methods: The experience of 24 participants was evaluated after 12 and 24 weeks of dietary intervention using survey responses and open questions. Results & conclusion: Retention rates for the WFKD and WFD groups were 93 and 89%, respectively. Average adherence to the WFKD was 82% and to the WFD was 87%. The WFKD enjoyment was rated at 66 and 81% for the WFD group. The ease of adhering to the diet varied more widely for the WFKD group. Barriers included knowledge integration, time management, navigating social food environments and emotional attachment to eliminated foods. Facilitators included structured support and coaching, and comprehensive learning materials. The WFKD was shown to be a feasible and effective treatment option for chronic pain.

This paper reports the experiences of 24 individuals with chronic pain when undertaking either a whole-food diet or a whole-food ketogenic diet as an intervention for their chronic pain. The diet ran for 12 weeks, and participants were surveyed at the end of the diet and again after another 12 weeks. There was a low dropout rate for both the groups, and participants reported adhering to the diet they were allocated to. Participants in the ketogenic group reported less enjoyment and were more varied in their adherence to the diet; however, the diet was shown to be feasible in this patient population. There were barriers to engaging with the diet including: implementing the rules of the diet, finding the extra time required, eating out and missing high carbohydrate foods. Having good information to follow and someone to coach them assisted participants to successfully implement the diet.

Dietary Interventions Are Beneficial for Patients with Chronic Pain: A Systematic Review with Meta-Analysis.

BACKGROUND: The standard Western diet is high in processed hyperpalatable foods that displace nutrient-dense whole foods, leading to inflammation and oxidative stress. There is limited research on how these adverse metabolic drivers may be associated with maladaptive neuroplasticity seen in chronic pain and whether this could be attenuated by a targeted nutritional approach. The aim of this study was to review the evidence for whole-food dietary interventions in chronic pain management. METHOD: A structured search of eight databases was performed up to December 2019. Two independent reviewers screened studies and evaluated risk of bias by using the National Institutes of Health assessment tool for controlled or pre-post studies and the Joanna Briggs checklist for case reports. A meta-analysis was performed in Review Manager. RESULTS: Forty-three studies reporting on 48 chronic pain groups receiving a whole-food dietary intervention were identified. These included elimination protocols (n = 11), vegetarian/vegan diets (n = 11), single-food changes (n = 11), calorie/macronutrient restriction (n = 8), an omega-3 focus (n = 5), and Mediterranean diets (n = 2). A visual analog scale was the most commonly reported pain outcome measure, with 17 groups reporting a clinically objective improvement (a two-point or 33% reduction on the visual analog scale). Twenty-seven studies reported significant improvement on secondary metabolic measures. Twenty-five groups were included in a meta-analysis that showed a significant finding for the effect of diet on pain reduction when grouped by diet type or chronic pain type. CONCLUSION: There is an overall positive effect of whole-food diets on pain, with no single diet standing out in effectiveness. This suggests that commonalities among approaches (e.g., diet quality, nutrient density, weight loss) may all be involved in modulating pain physiology. Further research linking how diet can modulate physiology related to pain (such as inflammation, oxidative stress, and nervous system excitability) is required.

Participants with chronic pain do not perceive diet as a contributing factor to their pain: a survey-based study.

Aim: To explore the reported diet of Australians with chronic pain and their perceived role of food within their pain experience. Methods: A cross-sectional study of 50 participants reporting chronic pain was undertaken using pain and nutritional questionnaires as well as anthropometric measures. Results: Participants rated their diet between 'good' and 'excellent' (76%) and one that promoted well-being (62%), however 74% were overweight or obese (average BMI 30) with multiple co-morbidities. There was no correlation between measures of dietary adherence and knowledge with reported pain. Conclusion: Participants generally reported their diets to be good, however, this was not reflected in their habitual diet. There was a low perceived role of food altering pain perception.

An evidence-based approach to developing low-carbohydrate diets for type 2 diabetes management: A systematic review of interventions and methods.

AIM: To identify core diet and delivery components of low-carbohydrate (CHO) diets that have demonstrated efficacy for type 2 diabetes (T2D) management. MATERIALS AND METHODS: MEDLINE, Pre-MEDLINE, EMBASE, CINAHL and the Cochrane Library of Controlled Trials databases were systematically searched from inception until August 18, 2018. Primary intervention studies of low-CHO diets (≤130 g/d or 26% total energy intake [TEI]) were included. Content analysis was performed on the low-CHO diet protocols classified as safe and effective for T2D management. RESULTS: A total of 41 studies published between 1963 and 2018 were included, of which 40 were classified as safe and effective for inclusion in the primary analysis. Thirteen studies (13/40) were on very-low-CHO diets (<50 g/d), 14/40 included low-CHO diets (≤130 g/d or 26% TEI), and 13/40 were adapted according to participant progress. Thirty-one studies reported a total energy prescription, of which 18/31 encouraged ad libitum intakes. Twenty studies reported a prescribed dietary fat amount, of which 18/20 were unrestricted or high-fat (>35% TEI). Twenty-six studies reported a prescribed dietary protein amount, of which 22 were unrestricted or were high-protein (>25% TEI). The types of dietary CHO, fat and protein recommended were predominantly whole foods. Common delivery methods reported were dietician and/or physician involvement, moderate to high frequency of contact (≥1 session/month) and use of participant self-monitoring. CONCLUSIONS: Multiple approaches for developing and delivering a low-CHO diet intervention for T2D management are safe and effective. A comprehensive set of core dietary components to consider in the formulation of low-CHO diet protocols were identified for use in clinical practice and to inform evidence-based guidelines for T2D management.