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1.
Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis.
Yuan, X, Wang, J, Yang, S, Gao, M, Cao, L, Li, X, Hong, D, Tian, S, Sun, C
Nutrition & diabetes. 2020;10(1):38
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Expert Review
Conflicts of interest:
None
Take Home Message:
A ketogenic diet may be a useful dietary intervention for type 2 diabetics with the potential to:
- Reduce fasting blood glucose
- Reduce HBA1c
- Reduce triglycerides, total cholesterol and LDL
- Increase HDL
- Promote weight loss
- Positive results were observed within in a minimum time frame of 1 week
Based on the findings, the ketogenic diet may prove beneficial as a component of an integrated approach for the management of type 2 diabetes.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Type 2 diabetes has become a worldwide health burden with a global prevalence of 300 million. Being overweight or obese has demonstrated to be a significant risk factor for the development of type 2 diabetes. The ketogenic diet which can be characterised by a diet of <55g of carbohydrates daily has demonstrated to be a beneficial intervention for weight loss and glycemic control suggesting potential utility for type 2 diabetics. This systematic review and meta-analysis compared the effects of a ketogenic diet on markers of glycemic control, lipid metabolism and body weight in type 2 diabetics pre and post intervention. There were a total of 13 studies and 567 subjects included in this meta-analysis. The findings conclude that type 2 diabetics following a ketogenic diet intervention ranging from 1-56 weeks experienced an average reduction of fasting blood glucose of 1.29mmol/l, HBA1c reduced by 1.07%, triglycerides decreased by 0.72 mmol/L , total cholesterol decreased by 0.33 mmol/L, LDL decreased by 0.05 mmol/L, HDL increased by 0.14 mmol/L, the average body weight decreased by 8.66 kg , waist circumference reduced by 9.17 cm and BMI reduced by 3.13 kg/m2.
Clinical practice applications:
This meta-analysis demonstrates that a ketogenic diet may be a useful dietary intervention to improve glycemic control, lipid metabolism and body weight in Caucasian type 2 diabetics. Positive results were seen within as little as 1 week.
Macronutrient ratios of included studies:
* Carbohydrates: <50g/d - 15g/d
● Protein: 20-28% or 1.5g/kg or 72-100g per day
● Fats: 58%-75% or to satiety
Adverse reactions to the ketogenic diet were mentioned in two of the studies. In the first study, fatigue, headache, nausea and vomiting were more common amongst the ketogenic diet group following 2 weeks of the intervention, while constipation and orthostatic hypotension were more commonly observed following 10 weeks. Symptoms of increased hunger, headache, nausea, vomiting, constipation and diarrhea were observed in subjects following a ketogenic diet in a second study. The symptoms were categorised as mild and not related to clinical practice.
Considerations for future research:
This meta-analysis only included 13 studies with primarily Caucasian patients due to limited available clinical trials. Further research is needed in order to determine risk/benefit of the ketogenic diet in type 2 diabetics amongst different populations and ethnic groups, particularly where type 2 diabetes is more prevalent. Follow-up periods ranged from 1-56 weeks. Longer-term studies would be useful to assess potential risks or benefits that would present over a longer time period.
Abstract
BACKGROUND At present, the beneficial effect of the ketogenic diet (KD) on weight loss in obese patients is generally recognized. However, a systematic research on the role of KD in the improvement of glycemic and lipid metabolism of patients with diabetes is still found scarce. METHODS This meta-study employed the meta-analysis model of random effects or of fixed effects to analyze the average difference before and after KD and the corresponding 95% CI, thereby evaluating the effect of KD on T2DM. RESULTS After KD intervention, in terms of glycemic control, the level of fasting blood glucose decreased by 1.29 mmol/L (95% CI: -1.78 to -0.79) on average, and glycated hemoglobin A1c by 1.07 (95% CI: -1.37 to -0.78). As for lipid metabolism, triglyceride was decreased by 0.72 (95% CI: -1.01 to -0.43) on average, total cholesterol by 0.33 (95% CI: -0.66 to -0.01), and low-density lipoprotein by 0.05 (95% CI: -0.25 to -0.15); yet, high-density lipoprotein increased by 0.14 (95% CI: 0.03-0.25). In addition, patients' weight decreased by 8.66 (95% CI: -11.40 to -5.92), waist circumference by 9.17 (95% CI: -10.67 to -7.66), and BMI by 3.13 (95% CI: -3.31 to -2.95). CONCLUSION KD not only has a therapeutic effect on glycemic and lipid control among patients with T2DM but also significantly contributes to their weight loss.
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2.
Zinc supplementation affects favorably the frequency of migraine attacks: a double-blind randomized placebo-controlled clinical trial.
Ahmadi, H, Mazloumi-Kiapey, SS, Sadeghi, O, Nasiri, M, Khorvash, F, Mottaghi, T, Askari, G
Nutrition journal. 2020;19(1):101
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Plain language summary
Migraine is a chronic neurovascular disorder. Patients with this disorder suffer from severe headaches and also nausea, vomiting, photophobia, and phonophobia during a migraine attack. Several supplementary treatments have been suggested for the management of migraine symptoms. Among these methods, there is the supplementation with micronutrients. The aim of this study was to examine the effect of zinc supplementation on characteristics of migraine attacks in migraine patients. This study is a double-blind randomized clinical trial which included migraine patients, with an age range between 20 and 60 years. Patients were stratified based on age (20–40 and 40–60 years), gender (male and female), and body mass index (18.5–24.9 and 25–30) into different blocks. Then, they were randomly allocated to the intervention or control groups. Results show that when compared to the placebo group, zinc supplementation resulted in a significant reduction in headache severity and migraine attacks frequency. However, the effect on headache severity became statistically non-significant when baseline values of headache severity and potential confounders were taken into account. Authors conclude that zinc supplementation was beneficial for migraine attack frequency but not for migraine attack duration and headache daily results.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Inadequate zinc intake may drive migraine frequency.
- Zinc supplementation may enhance the effectiveness of routine migraine treatment in reducing migraine frequency.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Migraines, characterised by severe headaches, nausea, vomiting, photophobia, and phonophobia affect approximately 10-20% of the global population. The authors refer to observational studies that have identified a moderate rate of zinc deficiency amongst migraine sufferers.
Zinc, an essential trace mineral, may prove beneficial as a supplement to reduce migraine symptoms and frequency possibly due to its effects on the nervous system and its antioxidant and anti-inflammatory capacity..
This double blind randomised clinical trial analysed the effects of 220mg of zinc sulphate (50mg of elemental zinc) combined with a routine migraine treatment versus a control group receiving a placebo and the routine treatment on symptoms of migraine attacks. The study duration was 8 weeks occurring from January 2016 to April 2016. Each group consisted of 40 participants between the ages of 20 and 60 with >5 years of migraines or migraine symptoms.
When compared to the placebo group, zinc supplementation demonstrated:
- A reduction in headache severity (− 1.75 ± 1.79 vs. -0.80 ± 1.57; P = 0.01). This result became statistically non-significant when the analysis was adjusted for potential confounders and baseline values of headache severity.
- A reduction in migraine attacks frequency (− 2.55 ± 4.32 vs. -0.42 ± 4.24; P = 0.02).
Clinical practice applications:
This randomised controlled trial highlights that zinc supplementation combined with routine migraine treatment (200/500 mg sodium valproate (such as Depakin), 50/100 mg sumatriptan, or 1 mg ergotamine) may assist in the reduction of migraine attack frequency amongst migraine sufferers within 8 weeks.
Compliance rate for this study was very high at 100% and there were no adverse effects reported suggesting a potentially safe and convenient treatment for migraine sufferers.
Considerations for future research:
- Further trials with better dietary controls would be useful to eliminate potential confounders.
- Use of CONSORT guidelines for reporting randomised trials would strengthen research reporting.
- Analysis of biomarkers may assist in identifying the mechanisms in which zinc may relieve migraine symptoms..
- Larger randomised controlled trials with increased sample sizes and longer durations are needed in order to definitively determine the effect of zinc supplementation on migraine attacks and any differences between genders.
- Additional studies trialling various zinc dosages and forms may provide insight into an optimal zinc dose and form for migraine attacks.
Abstract
BACKGROUND Observational studies have shown a link between zinc deficiency and migraine headaches. We aimed to examine the effect of zinc supplementation on the characteristics of migraine attacks in patients with migraine. METHODS This randomized clinical trial was conducted on 80 patients with migraine. Patients were randomly assigned to receive either zinc sulfate (220 mg/d zinc sulfate) or placebo (lactose) for 8 weeks. Anthropometric measures, serum zinc concentrations, and characteristics of migraine attacks (headache severity, frequency and duration of migraine attacks, and headache daily results) were assessed at baseline and end of the trial. RESULTS Compared with the placebo, zinc supplementation resulted in a significant reduction in headache severity (- 1.75 ± 1.79 vs. -0.80 ± 1.57; P = 0.01) and migraine attacks frequency (- 2.55 ± 4.32 vs. -0.42 ± 4.24; P = 0.02) in migraine patients. However, the observed reduction for headache severity became statistically non-significant when the analysis was adjusted for potential confounders and baseline values of headache severity. Other characteristics of migraine attacks including the duration of attacks and headache daily results were not altered following zinc supplementation either before or after controlling for covariates. CONCLUSION Zinc supplementation had a beneficial effect on the frequency of migraine attacks in migraine patients. Additional well-designed clinical trials with a long period of intervention and different dosages of zinc are required. TRIAL REGISTRATION CODE IRCT20121216011763N23 at www.irct.ir .
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3.
Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study).
Zhang, Y, Gu, Y, Ren, H, Wang, S, Zhong, H, Zhao, X, Ma, J, Gu, X, Xue, Y, Huang, S, et al
Nature communications. 2020;11(1):5015
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Plain language summary
Berberine, which is a naturally occurring alkaloid found in plants, has been traditionally used as a remedy to protect against Type 2 diabetes and other metabolic disorders. It is important to study how berberine affects the human gut microbiome, specifically in regard to its impact on short-chain fatty acid and bile acid metabolism, due to its low oral bioavailability. The PREMOTE study investigated the glycaemic lowering effects of individual and combination of berberine and probiotics in newly diagnosed Type 2 Diabetes patients. This randomised, double-blinded, placebo-controlled trial included four hundred and nine Type 2 diabetic patients and randomly assigned them (1:1:1:1 ratio) to receive berberine alone, berberine combined with probiotics, probiotics alone or a placebo for twelve weeks. A combination of berberine plus probiotics and berberine alone significantly improved glycated haemoglobin levels compared to the placebo and probiotics alone treatment. The antidiabetic effects of berberine could be due to the Ruminococcus bromii abundance followed by the berberine treatment and its ability to inhibit deoxycholic acid biotransformation. Further robust studies are required to consider the therapeutic application of berberine and probiotics in a general population due to the limitations of the present study. However, healthcare professionals can use the results of this trial to understand the mechanism behind the anti-diabetic effects of berberine and probiotics.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The use of berberine, as a specific antimicrobial agent, along with high strength probiotics may be beneficial for managing blood glucose and potentially other metabolic health markers alongside diet and lifestyle modifications
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Dysbiosis of the human gut microbiome has been associated with the development of type 2 diabetes (T2D). Research has found that, in part, mechanisms of action for the antidiabetic medications, Metformin and Acarbose, include alterations in the gut microbiome as well as the inhibition of bile acid (BA) metabolism and signalling. Remedies targeting the gut microbiota for treatment of T2D and other metabolic diseases have therefore been investigated.
Berberine (BBR) has been used in Indian Ayurvedic and Traditional Chinese Medicine to treat metabolic conditions for hundreds of years. Probiotics have also been extensively researched for their potential metabolic benefits. This randomised, double-blind, placebo-controlled trial aimed to investigate whether BBR and probiotics may be effective in managing T2D.
Methods
A total of 409 participants aged 42-61 years were recruited from 20 medical centres in China. All patients were newly diagnosed (<12 months) with T2D and had no previous antidiabetic medication history. Participants were randomised into 4 groups; Probiotics and BBR, BBR only, probiotics only or a placebo for 12 weeks. Subgroup analysis was also completed for those aged >50 and >54.
Dosage of BBR was 0.6 g prior to a meal, twice daily. 4 g of powdered multi-strain probiotics including 9 strains of lactic acid bacteria were taken at bedtime. All participants were given a 7-day broad-spectrum antibiotic treatment immediately prior to baseline. 391 people completed the trial. The primary outcome measurement was glycaemic haemoglobin (HbA1c). Secondary evaluations of additional metabolic markers included fasting and post-load plasma glucose (FPG, PPG), homeostasis assessment model index for insulin resistance (HOMA-IR), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) and serum triglycerides (TG).
Results
Results showed a reduction in glycaemic haemoglobin (HbA1c) for both the BBR plus probiotics group (least squares mean [95% CI] -1.04 [-1-19, -0.89]% ) and the BBR only group (-.99 [-1.16, 0.83]%). The results for these groups were significantly greater than the probiotics alone (-0.53 {-068, -0.37]%) and the placebo groups (0.59 [-0.75, -0.44]%).
Secondary metabolic evaluations for FPG and PPG, TC, LDL -c and TGs also showed similar improvements in the BBR and BBR plus probiotic groups only. Additionally, in the >50 and >54 subgroups BBR and probiotics marginally improved the HOMA-IR.
Metagenomic and metabolomic analysis of the gut microbiome was also undertaken after a one-week pre-treatment with antibiotics immediately prior to the trial and at week 13. These results showed that the blood glucose lowering effects of BBR may be due to decreased deoxycholic acid species (DCA) biotransformation by ruminococcus bromii.
Higher levels of adverse gastrointestinal side effects were reported in the BBR treatment groups, however, the authors reported that this did not affect glycemic control outcomes.
Conclusion
This study found that BBR had an antidiabetic effect through microbial alterations in the human gut microbiome
The authors declare no conflicts of interest.
Clinical practice applications:
- 600mg of BBR twice daily prior to a meal plus a multi-strain (lactic acid) probiotic of >50 billion colony forming units (CFU) for 12 weeks may be effective in lowering HbA1c in T2D clients diagnosed within the previous 12 months
- Further research is needed for clients with longer term T2D diagnosis
- Insulin resistance may be marginally improved in clients >50
- Practitioners should be aware that in this study, adverse gastrointestinal side effects were more likely to be be experienced with the use of BBR
Considerations for future research:
The authors reported several limitations to this study:
- A population of Chinese people living in China may not be generalisable to other ethnic/racial populations
- The study was over a short duration. Longer studies are needed to confirm the results
- Participants had newly diagnosed T2D and had not received any previous medications. Future studies should include patients with a longer diagnosis time
- Records should be kept of any additional lifestyle changes made by the participants
- Adverse reactions were experienced in the BBR groups, in this study. It was reported that the gut microbiome and anti-diabetic effects were not affected, however, this may be something to be considered in longer trials.
Abstract
Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], -1.04[-1.19, -0.89]%) and BBR-alone group (-0.99[-1.16, -0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (-0.59[-0.75, -0.44]%, -0.53[-0.68, -0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).
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4.
Investigating the nutritional advice and support given to colorectal cancer survivors in the UK: is it fit for purpose and does it address their needs?
Matsell, SL, Sánchez-García, MA, Halliday, V, Williams, EA, Corfe, BM
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2020;33(6):822-832
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Expert Review
Conflicts of interest:
None
Take Home Message:
- People with a cancer diagnosis affecting the digestive system may be in need of personalised advice on nutrition and lifestyle at several points in their cancer journey. Appropriately skilled and experienced nutrition professionals may meet this need and improve the patient experience.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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X
C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This descriptive cross-sectional study used a survey to explore the experience of people diagnosed with colorectal cancer (CRC), regarding the information they received on nutrition.
Methods
- The survey used a self-administered questionnaire. This was derived from a questionnaire developed by the National Institute for Health Research (NIHR) collaboration on nutrition and cancer to explore the patient experience of those diagnosed with cancer.
- Survey participants were recruited via cancer charities, social media and support groups, and were therefore self-selected.,
- The questionnaire used open-ended and closed questions to collect quantitative and qualitative data on patient characteristics and their perspectives on nutritional needs and nutritional advice. Participants could complete the questionnaire on-line or on paper.
- Statistical analysis of numerical data used SPSS software. Text data in response to open-ended questions were analysed using reflexive thematic analysis, with two researchers independently coding the text to identify emerging themes, which were then reviewed and summarised by the research team.
Participants
- 80 participants completed the survey, of which 5 were excluded due to non-CRC diagnoses. 75 eligible responses were analysed, 70 were completed by people diagnosed with CRC and 5 by a carer of a person with CRC.
- Participants came from all nine regions of the NHS, two-thirds were female, and 83% were aged 50 years and above.
- Dividing participants by stage of cancer determined that 44% had advanced cancer, the remaining being characterised as early, and tumour location at diagnosis were split equally between colon and rectum.
- For 12% of patients their diagnosis was a recurrence, and 45% had required a colostomy procedure. Stratified by treatment stage, 25% were in active treatment, 56% had completed treatment and were being monitored, and 17% were receiving symptomatic treatment only.
Findings
- Detailed data on nutritional problems experienced by participants were collected, of which diarrhoea was the most common, affecting 73% participants, secondly uncertainty about what to eat affected 70% participants.
- 69% of participants reported receiving no nutritional advice regarding their cancer from their NHS cancer care team. Reasons cited were ‘not offered advice’ (69%) ‘did not know it existed’ (45%) and did not know how to access it (24%).
- Of the participants who received nutritional advice for their CRC, 56% received this from a nurse, 26% from a specialist dietitian and 35% from a general dietitian.
- Advice received at the diagnosis stage was equally likely to be around physical activity and foods to avoid, Advice received during treatment included foods to eat or avoid and general healthy eating advice.
- Participants who reported receiving no nutritional advice from their care team were asked if they received advice elsewhere. Cancer support groups provided nutrition advice to 16% respondents but 70% received no advice from any other sources. Those who sought their own advice used charity websites, recipe books and social media, including Facebook groups, and patient blogs. On-line searches for nutrition advice were commonly reported by participants.
- Comments on hospital food were also submitted by some survey participants, of which there were more than twice the number of negative comments as positive.
Emerging themes
Three main themes emerged from the qualitative data analysis derived from participants’ responses:
- Theme 1: Lack of nutritional advice
- Theme 2: Individualised aid from healthcare professionals was highly valued
- Theme 3: Treatment side-effects and bowel function impairment hinder ability of following a healthy diet
Conclusions
The authors noted that less than one third of patients with a diagnosis of CRC received nutritional advice from a member of their care team, Advice received was not considered to meet expectations, being generic and unsuited to many individuals. CRC patients want individual advice, and from the professionals in their care teams, preferably from a dietitian.
Clinical practice applications:
- Personalised nutrition advice was considered important to the participants in this survey.
- This echoes findings of other researchers in this field, for example Penny Brohn UK, a Bristol-based charity supporting people affected by cancer.
- Evidence-based nutrition advice for people with a diagnosis of CRC may support recovery, and needs to be individualised, as a range of side effects and bowel symptoms appear to hinder recovery.
- Appropriately qualified and experienced nutrition professionals may provide this individualised advice.
Considerations for future research:
- This was a small survey and the self-selected sample cannot be considered representative, therefore the findings cannot be generalised to a wider population. Further research may consider random sampling or other survey sampling techniques to produce more representative data.
- Further qualitative research could include in-depth interviews or focus groups to explore themes in more depth, for example explore the long- term impact of personalised nutritional advice on people living with and beyond CRC.
- This study did not report whether participants had consulted other nutrition professionals outside the NHS. This is an area for future research.
Abstract
BACKGROUND The present study assessed the quantity and quality of nutritional advice and support given to colorectal cancer survivors in the UK. METHODS A descriptive cross-sectional survey was completed by 75 colorectal cancer survivors recruited through social media and bowel cancer support groups in the UK. The survey consisted of open-ended and closed questions that aimed to explore the nutritional needs, nutritional advice given and other sources of information accessed by colorectal cancer survivors. RESULTS Sixty-nine percent of respondents reported that they did not receive any nutritional advice or support from their healthcare team throughout diagnosis, treatment and post-treatment. Colorectal cancer survivors accessed nutritional advice from a variety of sources, mainly cancer charity websites. Respondents expressed their desire for individualised advice relating to their nutritional problems. CONCLUSIONS The results obtained in the present study indicate that a high proportion of colorectal cancer patients are not receiving the nutritional support that they need to overcome nutritional difficulties. There is an urgent need to improve clinical practice to ensure colorectal patients receive nutritional advice that is both consistent between healthcare professionals and personalised throughout each stage of diagnosis, treatment and post-treatment.
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5.
The effect of periodontal bacteria infection on incidence and prognosis of cancer: A systematic review and meta-analysis.
Xiao, L, Zhang, Q, Peng, Y, Wang, D, Liu, Y
Medicine. 2020;99(15):e19698
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Expert Review
Conflicts of interest:
None
Take Home Message:
- Oral health has implications beyond the mouth itself, and this study illustrates the association between periodontal bacterial infection and cancer
- People with periodontal infections are at greater risk of cancer and for poorer outcomes from cancer. Specific measures to support oral health may impact on cancer risk and outcomes.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- This systematic review/meta-analysis aimed to assess the effect of periodontal bacteria infection on cancer incidence/prognosis
- Following PRISMA guidelines, the authors screened four databases for clinical studies of periodontal bacterial infection and cancer incidence/outcomes. 38 studies encompassing 7184 participants met their criteria
- The presence of periodontal bacterial infection was associated with significantly increased incidence of cancer, with Odds Ratio (OR) of 1.25 (.95%CI: 1.03–1.52)
- Cancers were reported by tumour location and included cancers of the oesophagus, pancreas, colon and rectum, and oral cavity
- For people affected by cancer with periodontal bacterial infection, their overall survival was shorter than uninfected individuals with cancer, with Hazards Ratio (HR) of 1.75 (. 95% CI: 1.40–2.20)
- Furthermore, disease-free survival was significantly shorter (HR 2.18; 95%CI: 1.24–3.84) and cancer-specific survival was shorter (HR 1.85; 95%CI: 1.44–2.39)
- 23 of the studies included in the meta-analysis reported microbial species implicated in periodontal infection, with the strongest association with cancer seen in people with Porphyromonas gingivalis infection (OR 2.16), a common oral bacterium found in periodontal disease
- The strongest associations between periodontal bacterial infection and cancer outcomes were seen with colorectal and oesophageal cancers.
Clinical practice applications:
- Periodontal bacterial infection is common and increasingly recognised as impacting on other aspects of health beyond the mouth
- Systemic inflammation may be a route by which periodontal disease increases risks of other health conditions
- This analysis illustrates the relationship with cancer, which is also increasing across populations. Addressing oral health may have an important contribution to cancer prevention
- Practitioners working with people at particular risk of oesophageal or colorectal cancers may wish to consider oral health
- Nutritional interventions impacting on oral health have been reported elsewhere and include attention to the oral microbiome and tissue health.
Considerations for future research:
- Further research may confirm specific improvements in oral health that may impact on cancer risk
- Periodontal infection involving fungal species were not included in the analysis and the authors acknowledge this is another aspect of periodontal infection worthy of study.
Abstract
BACKGROUND Periodontal bacteria is the major pathogens in the oral cavity and the main cause of adult chronic periodontitis, but their association with incidence and prognosis in cancer is controversial. The aim of this study was to evaluate the effect of periodontal bacteria infection on incidence and prognosis of cancer. METHODS A systematic literature search of PubMed, Embase, Web of Science, and Cochrane Library databases was performed to obtain 39 studies comprising 7184 participants. The incidence of cancer was evaluated as odd ratios (OR) with a 95% confidence interval (95% CI) using Review Manager 5.2 software. Overall survival, cancer-specific survival and disease-free survival, which were measured as hazard ratios (HR) with a 95% CI using Review Manager 5.2 software. RESULTS Our results indicated that periodontal bacteria infection increased the incidence of cancer (OR = 1.25; 95%CI: 1.03-1.52) and was associated with poor overall survival (HR = 1.75; 95% CI: 1.40-2.20), disease-free survival (HR = 2.18; 95%CI: 1.24-3.84) and cancer-specific survival (HR = 1.85, 95%CI: 1.44-2.39). Subgroup analysis indicted that the risk of cancer was associated with Porphyromonas gingivalis (Pg) infection (OR = 2.16; 95%CI: 1.34-3.47) and Prevotella intermedia (Pi) infection (OR = 1.28; 95%CI: 1.01-1.63) but not Tannerella forsythia (Tf) (OR = 1.06; 95%CI: 0.8-1.41), Treponema denticola (Td) (OR = 1.30; 95%CI: 0.99-1.72), Aggregatibacter actinomycetemcomitans (Aa) (OR = 1.00; 95%CI: 0.48-2.08) and Fusobacterium nucleatum (Fn) (OR = 0.61; 95%CI: 0.32-1.16). CONCLUSION This meta-analysis revealed periodontal bacteria infection increased the incidence of cancer and predicted poor prognosis of cancer.
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6.
Gut feelings: A randomised, triple-blind, placebo-controlled trial of probiotics for depressive symptoms.
Chahwan, B, Kwan, S, Isik, A, van Hemert, S, Burke, C, Roberts, L
Journal of affective disorders. 2019;253:317-326
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Plain language summary
Depression is a debilitating psychiatric disorder that is the leading cause of disability world-wide. Multiple causes of depression have been identified, including genetic, neurological, inflammatory, personality, cognitive, and environmental factors. The aim of this study was to investigate the effectiveness of the multispecies probiotic Ecologic® Barrier for reducing symptoms in adults with mild to severe levels of depression. The study was a triple-blinded parallel, placebo-controlled randomised clinical trial. Participants were randomly allocated into two groups; probiotic and placebo. 71 participants with depressive symptoms were recruited and allocated sequentially over 12 months. Results indicate that all participants across both probiotic and placebo groups exhibited a reduction in depressive symptoms over the time-period of the trial. Thus, the routine involved with daily preparation and consumption of the probiotic and scheduled appointments, as well as involvement in these behaviours with the aim of seeking improvement in depressive symptoms had positive impacts on mood, irrespective of whether the probiotic or placebo was consumed. Authors conclude that their findings offer evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This study offers evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression.
- The study suggests that probiotics, rather than having a direct effect on depressive symptoms, potentially act on immune system activity, inflammation and gut barrier integrity which contribute to the expression of depression.
- Probiotics may be a useful adjunct to potentiate the effects of other therapies, such as CBT.
- This study points to the validity of managing physical health as part of mental health treatment.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
With evidence suggesting that decreased gut barrier function and inflammation are correlated with depression, this study set out to determine the effect of consumption of probiotic supplements on depressive symptoms from a sample of 71 participants with depression. The study was a triple-blinded parallel, placebo-controlled randomised clinical trial conducted over 8 weeks in Australia. Pre and post intervention measures of symptoms and vulnerability markers of depression as well as gut microbiota were compared alongside psychological variables and gut microbiota composition to non-depressed, placebo and probiotic groups. All the clinical trial participants demonstrated an improvement in symptoms – participants in the probiotic group demonstrated a significantly greater reduction in cognitive reactivity compared with the placebo group. Probiotics did not significantly alter the microbiota of depressed individuals, however a significant correlation was found between Ruminococcus gnavus and one of the metrics for depression.
Clinical practice applications:
This study was small and carried out over a short period of time. While significant results were found, which signify potential considerations for clinical practice, the results from this study do not offer evidence that the probiotics used had a direct effect on depressive symptoms – they suggest that probiotics potentially act on cognitive processes contributing to depression which may include immune system activity, inflammation, and gut barrier integrity. Overall, this study offers evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression. In clinical practice, probiotics may be a useful adjunct to potentiate the effects of therapies, such as CBT. Finally, the use of probiotics promotes the concept of managing physical health as part of mental health treatment.
Considerations for future research:
These preliminary results are promising and offer a number of future research and clinical avenues to build upon. The results do however, indicate that a longer trial may be needed to fully assess the effects of probiotics on mood and the mechanisms by which probiotics may be influencing this. The study also suggests that further research using a range of concentrations in a dose response study may be warranted to determine the optimal dose; a greater dose over a longer period may produce detectable changes in microbiota as well as further differences in psychological data.
Abstract
BACKGROUND Depression is the leading cause of disability worldwide; with evidence suggesting that decreased gut barrier function and inflammation are correlated with depressive symptoms. We conducted a clinical trial to determine the effect of consumption of probiotic supplements (Winclove's Ecologic® Barrier) on depressive symptoms in a sample of participants with mild to severe depression. METHOD 71 participants were randomly allocated to either probiotic or placebo, which was, consumed daily over eight weeks. Pre- and post-intervention measures of symptoms and vulnerability markers of depression as well as gut microbiota composition were compared. Clinical trial participants were also compared on psychological variables and gut microbiota composition to a non-depressed group (n = 20). RESULTS All clinical trial participants demonstrated improvement in symptoms, suggesting non-specific therapeutic effects associated with weekly monitoring visits. Participants in the probiotic group demonstrated a significantly greater reduction in cognitive reactivity compared with the placebo group, particularly in the mild/moderate subgroup. Probiotics did not significantly alter the microbiota of depressed individuals, however, a significant correlation was found between Ruminococcus gnavus and one depression metric. LIMITATIONS There was a high attrition rate, which may be attributed to weekly monitoring visits. Additionally, modulation of the gut microbiota may need more specific testing to distinguish subtle changes. CONCLUSIONS While microbiota composition was similar between all groups, probiotics did affect a psychological variable associated with susceptibility to depression. Further research is needed to investigate how probiotics can be utilised to modify mental wellbeing, and whether they can act as an adjunct to existing treatments.
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7.
Broccoli consumption affects the human gastrointestinal microbiota.
Kaczmarek, JL, Liu, X, Charron, CS, Novotny, JA, Jeffery, EH, Seifried, HE, Ross, SA, Miller, MJ, Swanson, KS, Holscher, HD
The Journal of nutritional biochemistry. 2019;63:27-34
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Plain language summary
Diet affects metabolic and gastrointestinal diseases, with the microbiome considered to be a mediating factor. Broccoli is a good source of fibre and phytochemicals including glucosinolates. The aim of this investigator-blinded, controlled feeding, randomised, crossover study was to evaluate the effects of broccoli on the composition and function of the microbiome. 18 healthy adults received 200 g cooked broccoli and 20 g raw daikon radish per day for 18 days in addition to a controlled, brassica-free diet or the same diet without the broccoli and daikon radish, with a 24-day washout period. A statistically significant increase in the ratio of Bacteroidetes to Firmicutes was observed following the broccoli intervention. When stratified by BMI above or below 25, this increase was only seen in those with a lower BMI whilst those with a higher BMI displayed a decrease in the ratio, although the latter was not statistically significant. In those with the lower BMI, there was also a correlation between the changes in the microbiota composition and glucosinolate metabolites. It was predicted that the involved changes would affect the functions of the endocrine system, transport and catabolism and energy metabolism. The authors concluded that eating broccoli may affect both the composition and the function of the microbiome.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Broccoli consumption at dosages of 200g per day were shown to change the composition of gastrointestinal microbiota, increasing Bacteroidetes and decreasing Firmicutes, and impact their function
- The observed results were strongest in those with a BMI of less than 26
- While interesting, the study only included 18 participants and therefore the results should be further confirmed.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
There is growing evidence linking dysbiosis of the gastrointestinal microbiota and diet-induced gastrointestinal and metabolic diseases. Both long-term and acute dietary changes, fasting, eating frequency, and consumption of specific fibres and food phytochemicals play a role in shaping the composition and function of the microbiota, although evidence is lacking for specific foods. This study aimed to determine the impact of broccoli intake on the number of bacterial strains and their functional capacity.
Methods
This was a single-blind, randomised, crossover, complete feeding intervention. Study participants were healthy adults (n=18, females =10). Participants were requested to not eat Brassica vegetables for 3 weeks before the start of the study.
Subjects participated in two 18-day diet periods separated by a 24-hour washout, during which breakfast and dinner were consumed on site to observe compliance. The control diet was prepared using traditional American foods, excluding all Brassica vegetables. During the broccoli intervention period, participants consumed the same base diet with the addition of 200g of broccoli.
Faecal samples were collected on day 1, and day 16. Quantitative polymerase chain reaction was performed on bacterial strains. On day 17, time series plasma sampling and 24-hour urine collection was done.
Results
There was no difference in alpha diversity (a measure of microbiome diversity within a sample) between the two treatment periods. This indicates that no bacterial species were extinguished by broccoli treatment. Beta diversity analysis (a measure of the (dis)similarity between samples) indicated that bacterial communities were impacted by treatment (P=0.03).
After broccoli consumption, Bacteroidetes increased by 10% (P =0.03), while Firmicutes decreased by 8% (P=0.05). Overall the ratio of Bacteroidetes to Firmicutes increased by 37% (P=0.01) versus a 5% decrease in the control period. The Bacteroides genus increased by 6% (P=0.02) versus a 2% decrease in the control period.
Interestingly, the effects were most strong in those with a lower BMI (< 26 kg/m2) who had an increase in metabolites after broccoli consumption. Algorithms to predict the function of the microbiota showed that broccoli increased endocrine (P=0.05), energy metabolism (P=0.01), transport and catabolism (P=0.04) pathways.
Conclusion
Broccoli intake, at 200g daily, changes the composition and potentially impacts the function of the gut microbiota.
Clinical practice applications:
- Studies like this allow practitioners to focus on specific foods in specific quantities to positively alter the microbiota and their function
- Cruciferous vegetables, like broccoli, kale, cauliflower, cabbage, Brussel sprouts, are an important group as they contain fibre and phytonutrients such as glucosinolates. These compounds can be metabolised by the microbiota into active compounds with health benefits. This study has shown the bidirectional benefit of broccoli consumption in that it can positively impact the function and composition of the microbiota
- Interestingly, the results in this small study were driven by participants with a BMI of less than 26. Sub-group analysis found no statistically significant relationships in participants with BMI >26
- It is worth noting that it is possible that the addition of 5g of fibre from the broccoli is also contributing to the changes observed.
Considerations for future research:
- Larger, controlled feeding studies that isolate specific foods to identify their effects on the microbiota are needed
- Genetic sequencing for only a few bacterial myrosinases has been completed and therefore future studies should aim to assess the metabolic capabilities in faecal samples such as myrosinase activity
- While this study and others have shown changes in the types of bacteria after cruciferous vegetable consumption the consistency of results has been mixed potentially due to differing study designs and treatment dosages. Further studies to clarify and confirm these results would be beneficial
- To assess the function of the microbiota a predictive algorithm was used. This requires experimental confirmation by such methods as metabolite profiling and whole genome shotgun sequencing.
Abstract
The human gastrointestinal microbiota is increasingly linked to health outcomes; however, our understanding of how specific foods alter the microbiota is limited. Cruciferous vegetables such as broccoli are a good source of dietary fiber and phytonutrients, including glucosinolates, which can be metabolized by gastrointestinal microbes. This study aimed to determine the impact of broccoli consumption on the gastrointestinal microbiota of healthy adults. A controlled feeding, randomized, crossover study consisting of two 18-day treatment periods separated by a 24-day washout was conducted in healthy adults (n=18). Participants were fed at weight maintenance with the intervention period diet including 200 g of cooked broccoli and 20 g of raw daikon radish per day. Fecal samples were collected at baseline and at the end of each treatment period for microbial analysis. Beta diversity analysis indicated that bacterial communities were impacted by treatment (P=.03). Broccoli consumption decreased the relative abundance of Firmicutes by 9% compared to control (P=.05), increased the relative abundance of Bacteroidetes by 10% compared to control (P=.03) and increased Bacteroides by 8% relative to control (P=.02). Furthermore, the effects were strongest among participants with body mass index <26 kg/m2, and within this group, there were associations between bacterial relative abundance and glucosinolate metabolites. Functional prediction revealed that broccoli consumption increased the pathways involved in the functions of the endocrine system (P=.05), transport and catabolism (P=.04), and energy metabolism (P=.01). These results reveal that broccoli consumption affects the composition and function of the human gastrointestinal microbiota.
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8.
Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans.
Stekovic, S, Hofer, SJ, Tripolt, N, Aon, MA, Royer, P, Pein, L, Stadler, JT, Pendl, T, Prietl, B, Url, J, et al
Cell metabolism. 2019;30(3):462-476.e6
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Intermittent fasting and calorie restriction are believed to reduce cardiometabolic risk factors and increase longevity. Fasting alternate days (ADF) involves fasting for 36 hours and eating ad libitum for 12 hours. Thirty healthy participants were randomly assigned to a long-term ADF intervention group for ≥6 months against sixty participants in the control group. After completing the cross-sectional study arm, sixty healthy participants in the control group were randomly assigned to either a four-week short-term ADF intervention group or a control group with an ad libitum diet. Study participants adhered well to the fasting regimen. Both short-term and long-term ADF intervention groups showed a significant reduction in calorie intake, improvements in anthropometric and cardiovascular parameters including reduced BMI, substantial reduction in trunk fat, lower heart rate, increased serum β-hydroxybutyrate which is cardioprotective and anti-ageing, reduced circulating triiodothyronine (fT3) levels which indicate longevity. Short-term ADF reduced systolic and diastolic pressure, mean arterial pressure, pulse pressure, and pulse wave velocity. Long-term ADF intervention reduced circulating total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglycerides, the age-related biomarker sICAM-1 for disease and inflammation, and improved lipid and amino acid metabolites. ADF did not affect insulin sensitivity. Although red blood cells and iron levels were altered, ADF interventions were not associated with iron deficiency. Healthcare professionals can use the results of this study to understand the cardioprotective and anti-ageing properties of ADF. However, further long-term robust studies are required to evaluate the effect of long-term ADF on bone health.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Short duration (<4 weeks) alternate day fasting may be an effective way to implement caloric restriction, improve body composition and reduce cardiovascular disease risk in healthy non-overweight adults.
- >6 months alternate fasting does not appear to be associated with reduced bone mass, bone mineral density of the lumbar spine region, white blood cell counts, ferritin and transferrin when compared to healthy controls.
- Both short term and long term alternate day fasting may reduce triiodothyronine in healthy adults. Low levels of fT3 without thyroid gland dysfunction has been associated with longevity in humans.
- Alternate day fasting should be performed alongside a trained clinician to reduce the risk of adverse effects due to critical medical conditions.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Animal models have consistently demonstrated the healthspan and lifespan benefits of caloric restriction. However, chronic caloric restriction in humans has proven difficult to maintain.
Intermittent fasting may serve as a more manageable alternative to continuous caloric restriction. This randomised controlled trial and cross sectional analysis aimed to investigate the effects of alternate day fasting (ADF) on heart rate, blood pressure, cholesterol levels, CVD risk, body composition, and the metabolome and proteome of healthy, non-overweight adults (cohort median age between 48 and 52 years).
Methods
Prior to the enrollment of the study a cross sectional analysis was conducted on healthy adults engaged in long term (>6 months) alternate day fasting (n=30) and a control group (n=60).
The 60 participants from the cross sectional analysis control group were then randomised to either a 4 week ADF group or a control group. In both the >6 months and 4 weeks of ADF groups, participants were instructed to eat every second-day ad libitum, but to completely exclude solid and liquid foods and caloric beverages on fasting days.
Results
The cross sectional analysis identified that the alternate day fasting group:
- Consumed fewer calories vs the control group (−28.56%, p=0.0002).
- Had lower levels of circulating total cholesterol (p=0.004), LDL (p=0.011), VLDL (p=0.009), triglycerides (p=0.010) and a lower heart rate (p=0.040) vs the control group.
- Lower levels of soluble intercellular adhesion molecule-1 (sICAM-1) (p value 0.048), an age-associated inflammatory marker.
- Reduced circulating triiodothyronine (p<0.001) compared to the control group.
- In the metabolome, 54 out of 113 detected significantly modified metabolites (p value < 0.05) were at least 20% higher after 36 h of fasting, of which the majority (>95%) were lipids or free fatty acids, including polyunsaturated free fatty acids (PUFAs), α-tocopherol, and a type of vitamin E. 49 metabolites were at least 20% lower, consisting mainly (44.9%) of amino acids or related metabolites. Low levels of circulating amino acids have been found to increase lifespan in model organisms. The authors concluded that the elevation in fatty acids may be due to increased lipolysis from adipose tissue while the reduction in amino acids may be the result of increased gluconeogenesis.
- 13 out of 2,089 significantly (p value < 0.05) modulated protein hits within the PBMC proteome showed an increase of ≥15%, while the remaining proteins were downregulated after 36 h of fasting. Gene set enrichment analysis (GSEA) performed on the PBMC proteome unveiled changes in pathways related to lipid metabolism, pathways related to energy metabolism and stress response.
Following the 4 week intervention the alternate day fasting group demonstrated:
- Reduced caloric intake from baseline vs. the control group (−37.40% vs. −8.22%, p=0.0012).
- Greater reductions in body weight (−3.5kg vs −0.2kg, p<0.0001), BMI (−1.23kg/m2 vs −0.02kg/m2, p<0.0001) and improvements in their fat to lean mass ratio (−6.3% ± 5.0 percentage points, p value < 0.0001).
- Reduced systolic (−4.5mmHg, p=0.006) and diastolic (−2.5mmHg, p=0.03) blood pressure, heart rate (-4.5 b/min, p=0.0019), arterial (−3mmHg, p=0.0087) and pulse pressure (−2.5mmHg, p=0.0088) as well as pulse wave velocity (−1.538%, p=0.0362). Pulse wave velocity measures the rate at which pressure moves down the vessel wall and is a measure of arterial stiffness.
- Reduced circulating triiodothyronine (p<0.001) from baseline values.
Clinical practice applications:
The cross sectional analysis did not identify any differences in the long-term (>6 months) alternate day fasting group and control group in bone mass, bone mineral density of the lumbar spine region, white blood cell counts, ferritin and transferrin when compared to healthy controls. RBC counts and iron metabolism markers in the blood plasma (hematocrit, haemoglobin, iron, and transferrin saturation), were lower in the >6 months of ADF group but stayed within the reference range.
The randomised controlled trial demonstrated that alternate day fasting may be an effective intervention to reduce caloric intake, improve body composition and reduce cardiovascular disease risk in healthy non-overweight adults within 4 weeks.
Compliance rate was high with only 1 drop out in the alternate day fasting group of the randomised controlled trial.
Both the 4 week intervention and long-term (>6 month) analysis identified a reduction in triiodothyronine amongst the ADF groups. Low levels of triiodothyronine in absence of thyroid gland dysfunction has been associated with longevity in humans.
Considerations for future research:
- Future larger studies in non-healthy and/or overweight/obese populations would be useful to determine safety and efficacy of alternate day fasting within that population group.
- Further studies comparing alternate day fasting with continuous caloric restriction would be useful to identify which intervention is most beneficial for body composition and cardioprotection.
- Subgroup analysis of diet composition and diet quality may help to identify the most appropriate/inappropriate diet to compliment alternate day fasting.
- Longer duration randomised controlled trials are needed to identify any health risks or deficiencies which may develop with long term caloric restriction and alternate day fasting.
Abstract
Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after >6 months. ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-to-lean ratio, and increased β-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention.
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9.
Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study.
Rudzki, L, Ostrowska, L, Pawlak, D, Małus, A, Pawlak, K, Waszkiewicz, N, Szulc, A
Psychoneuroendocrinology. 2019;100:213-222
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Expert Review
Conflicts of interest:
None
Take Home Message:
- Significant improvement in cognitive performance and decreased l-tryptophan breakdown may be seen in patients on SSRI medication for depression, when supplemented with Lactobacillus Plantarum 299v.
- Work on microbiome diversity and gut barrier integrity may be important for psychiatric disorder support, including depression.
- More research is needed given small sample size and short trial period, with a focus on microbiome modulation over a longer period of time.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This study sets out to explore the psychobiotic potential of the probiotic strain Lactobacillus Plantarum 299v (LP299v), a common single strain probiotic supplement. Depression symptoms, cognitive function and biochemical parameters were assessed in 79 patients with MDD undergoing conventional treatment with SSRIs in this double-blind placebo-controlled trial over a period of 8 weeks. Various outcome measures were used to assess the severity of depression and cognitive function, and various biochemical parameters such as tryptophan, kynurenine and cortisol were monitored. Results showed there was a significant decrease in kynurenine concentration and an improvement in cognitive function in the LP299v group compared to placebo.
Clinical practice applications:
The small sample size and short trial period of 8 weeks are limitations to this study, however, the results are important and certainly warrant more research in this area. A focus on microbiome modulation over a longer period of time may be useful to give us insight into the multidirectional interactions of the gastrointestinal microbiome and the central nervous system.
Considerations for future research:
This study suggests that patients being treated with SSRIs for MDD may see a significant improvement in cognitive performance and a decrease in the breakdown of the important amino acid l-tryptophan (from the decrease in kynurenine concentration results) if they supplement with LP299v alongside. Therefore, consideration of the microbiome and gut barrier integrity with regard to psychometric and biochemical parameters could be important to support psychiatric disorders, including depression.
Abstract
BACKGROUND Interactions between the digestive system and the brain functions have become in recent years an important field of psychiatric research. These multidirectional interactions take place in the so called microbiota-gut-brain axis and emerging scientific data indicate to the significant role of microbiota in the modulation of the central nervous system (CNS) including affective and cognitive functions. OBJECTIVE An assessment of psychobiotic and immunomodulatory effects of probiotic bacteria Lactobacillus Plantarum 299v (LP299v) by measuring affective, cognitive functions and biochemical parameters in patients with MDD undergoing treatment with selective serotonin reuptake inhibitors (SSRI). DESIGN Seventy nine patients with MDD were randomized and allocated to a double-blind, placebo-controlled trial. Participants received either a SSRI with the probiotic LP299v (n = 40) for a period of 8 weeks or a SSRI with the placebo of the probiotic (n = 39) for the same period. The severity of psychiatric symptoms was assessed using Hamilton Depression Rating Scale (HAM-D 17), Symptom Checklist (SCL-90) and Perceived Stress Scale (PSS-10). Cognitive functions were assessed using the Attention and Perceptivity Test (APT), Stroop Test parts A and B, Ruff Figural Fluency Test (RFFT), Trail Making Test (TMT) Parts A and B and the California Verbal Learning Test (CVLT). Biochemical parameters such as tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3HKYN), anthranilic acid (AA), 3-hydroxy anthranilic acid (3HAA), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1-beta (IL-1b) and cortisol plasma concentrations were measured. RESULTS Sixty participants finished the study and were analyzed: 30 participants in the LP299v group and 30 participants in the placebo group. There was an improvement in APT and in CVLT total recall of trials 1-5 in the LP299v group compared with the placebo between baseline and after 8 weeks of intervention. There was a significant decrease in KYN concentration in the LP299v group compared to the placebo group. We also observed significant increase in 3HKYN:KYN ratio in the LP299v group compared with the placebo group. Additionally, Repeated Measures ANOVA revealed a significant effect of interaction of Treatment x time for AA concentration. However, results of post hoc analysis did not reach statistical significance in neither probiotic nor placebo group. There were no significant changes of TNF-α, IL-6 and IL-1b and cortisol concentrations in neither probiotic nor placebo groups. CONCLUSIONS Augmentation of SSRI treatment with probiotic bacteria Lactobacillus Plantarum 299v improved cognitive performance and decreased KYN concentration in MDD patients. Decreased KYN concentration could contribute to the improvement of cognitive functions in the LP299v group compared to the placebo group. To our knowledge results of this study are the first evidence of improvement of cognitive functions in MDD patients due to probiotic bacteria and this is the first evidence of decreased KYN concentration in MDD patients due to probiotic bacteria.
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10.
Meta-analysis of the effects of third-wave behavioural interventions on disordered eating and body image concerns: implications for eating disorder prevention.
Linardon, J, Gleeson, J, Yap, K, Murphy, K, Brennan, L
Cognitive behaviour therapy. 2019;48(1):15-38
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Expert Review
Conflicts of interest:
None
Take Home Message:
- Third wave behavioural interventions, such as acceptance and commitment therapy, dialectical behaviour therapy, mindfulness-based interventions and compassion-focused therapy are increasing in popularity and may be useful in both eating disorder treatment and prevention.
- Prevention of eating disorders is likely to be more cost-effective than treatment. Healthcare practitioners should be mindful of considering third wave interventions in their client referrals.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Third wave behavioural interventions are increasing in popularity and this meta-analysis provides evidence that they may be useful in both eating disorder treatment and prevention.
Eating disorders have a complex and poorly understood aetiology, which makes their treatment and prevention a challenge for public health. Third-wave interventions for eating prevention disorders provide a promising approach that can be delivered through various means including digitally.
Clinical practice applications:
Prevention of eating disorders is likely to be more cost-effective than treatment, and practitioners should be mindful of considering third-wave interventions in their client referrals. This should include those at risk of eating disorders (e.g. displaying a poor body image) as well as those with these conditions.
Considerations for future research:
As third wave interventions increase in popularity, further evidence is needed in the form of robust and valid trials to explore their value - particularly in terms of eating disorder prevention. Research is also needed on their application alongside other traditional therapies including those involving nutrition interventions.
Abstract
Third-wave behavioural interventions are increasingly popular for treating and preventing mental health conditions. Recently, researchers have begun testing whether these interventions can effectively targeting eating disorder risk factors (disordered eating, body image concerns). This meta-analysis examined whether third-wave behavioural interventions (acceptance and commitment therapy; dialectical behaviour therapy; mindfulness-based interventions; compassion-focused therapy) show potential for being effective eating disorder prevention programs, by testing their effects on eating disorder risk factors in samples without an eating disorder. Twenty-four studies (13 randomized trials) were included. Most studies delivered selective prevention programs (i.e. participants who reported elevated risk factor). Third-wave interventions led to significant pre-post (g = 0.59; 95% CI = 0.43, 0.75) and follow-up (g = 0.83; 95% CI = 0.38, 1.28) improvements in disordered eating, and significant pre-post improvements in body image (g = 0.35; 95% CI = 0.13, 0.56). DBT-based interventions were associated with the largest effects. Third-wave interventions were also significantly more efficacious than wait-lists (g = 0.39; 95% CI = 0.09, 0.69) in reducing disordered eating, but did not differ to other interventions (g = 0.25; 95% CI = -0.06, 0.57). Preliminary evidence suggests that third-wave interventions may have a beneficial effect in ameliorating eating disorder risk.