1.
Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.
Xia, J, Yu, J, Xu, H, Zhou, Y, Li, H, Yin, S, Xu, D, Wang, Y, Xia, H, Liao, W, et al
Pharmacological research. 2023;188:106647
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Type 2 diabetes mellitus (T2DM), characterised by sustained hyperglycaemia and insulin resistance, remains a severe driver of chronic metabolic diseases such as cardiovascular diseases. The aim of this study was to investigate and compare the efficacy of vitamin and mineral supplements in the management of glycaemic control and lipid metabolism for type 2 diabetic patients to inform clinical practice. This study is a systematic review and meta-analysis of one hundred and seventy articles with a total of 4223 adults with T2DM. Participants were randomised to either the placebo/no treatment group (n= 6345) or to the treatment group (n= 7878). Results show that: - chromium was the most effective micronutrient for decreasing fasting blood glucose and insulin resistance. - vitamin K was the top-ranked micronutrient in reducing haemoglobin A1C and fasting insulin levels. - vanadium was the top-ranked micronutrient in total cholesterol reductions. - niacin was ranked as the most effective in triglycerides reductions and increasing high-density lipoprotein cholesterol levels. - vitamin E was the top-ranked micronutrient in low-density lipoprotein cholesterol reductions. Authors conclude that micronutrient supplements especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more effective in the management of T2DM compared with other micronutrients.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Clinicians could consider the adjunctive effect of micronutrients supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements in a nutrition protocol to manage T2DM and slow or prevent its complications.
- The study authors state that the vitamin and mineral supplements under review had a statistically significant improvement, however they did not reach the study threshold for clinical significance. Therefore they advise caution in utilising micronutrient supplements in the management of glucose and lipid metabolism for T2DM.
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:
Objectives
The aim of this systematic review was to evaluate the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM).
Methodology
This systematic review is registered with PROSPERO and adhered to PRISMA-2020 guidelines for network meta-analysis
The Cochrane Collaboration’s risk-of-bias tool was used to assess eligible randomised trials
8 prespecified markers identified and assessed in this study : 1) HbA1c (%), 2) fasting blood glucose (mmol/L), 3) total cholesterol (mmol/L), 4) triglycerides (mmol/L), 5) fasting insulin (μIU/mL), 6) HOMA-IR, 7) LDL-c (mmol/L), and 8) HDL-c (mmol/L).
Results
- 170 RCT trials of 14223 participants with T2DM treated with vitamin supplements, mineral supplements, or placebo/no treatment were included
- Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively)
- Vitamin K supplements ranked best in reducing glycated haemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence
- Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%)
- Niacin supplements ranked best in triglyceride reductions and increasing high-density lipo-protein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively)
- Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%).
Conclusion
- Micronutrient supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be efficacious in managing T2DM
- It should be noted that the evidence certainty for all was low.
Clinical practice applications:
- Chromium plays an important role in carbohydrate and lipid metabolism and was the most effective micronutrient for decreasing fasting blood glucose, HbA1c, fasting insulin, and HOMA-IR reductions. More pronounced effects were seen for chromium than vitamin E, vitamin C, niacin, selenium, and magnesium supplements
- Vitamin K was the top-ranked micronutrient in reducing HbA1c and fasting insulin levels. The mechanism through which Vitamin K affects glucose metabolism is proposed as activation of the AMP-activated protein kinase/sirtuin 1, that in turn increases phosphocreatine 3-kinase and glucose transporter 2 to decrease insulin resistance and fasting glucose.
- Vanadium was the top-ranked micronutrient in total cholesterol (TC) reductions, where supplementation dosage should be carefully considered, as vanadium compounds can be moderately or highly toxic. Vanadium supplementation is only recommended in cases of vanadium deficiency or diabetes, hyperlipidemia, and hypertension, where the intake of vanadium from food should be enhanced in preference to supplementation
- Niacin was ranked as the most effective in triglyceride (TG) reductions and increasing HDL cholesterol levels. The dose of niacin could not be determined
- Vitamin E was the top-ranked micronutrient in low-density lipo- protein (LDL) cholesterol reductions.
Considerations for future research:
- Considering the clinical importance of these findings, new research is needed to get better insight into the efficacy of micronutrient supplements in managing T2DM
- Selenium homeostasis, selenoprotein, insulin signaling/secretion, and carbohydrate/lipid metabolism are linked in multiple and complex ways but the authors could not explain why chromium supplementation would lower blood glucose more effectively than selenium supplementation, and suggest more research is needed to clarify this
- While vitamin K status could be an emerging treatment target in T2DM prevention and management, it remains to be determined whether vitamin K supplementation has an advantage over other nutrients in terms of hypoglycemic effect, and further research is necessary
- The beneficial effect of vitamin E and niacin supplements regarding lipid metabolism warrant investigation through more rigorous comparative studies.
Abstract
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
2.
Distribution of energy intake across the day and weight loss: A systematic review and meta-analysis.
Young, IE, Poobalan, A, Steinbeck, K, O'Connor, HT, Parker, HM
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2023;24(3):e13537
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Obesity increases an individual's risk of metabolic disease, such as diabetes and cardiovascular disease, musculoskeletal disorders such as osteoarthritis, and some cancers. “Chrononutrition” relates to the timing of meals and distribution of total energy intake across the day. Evidence is building chrononutrition as a potential target in both weight loss and metabolic disease interventions. The aim of this study was to examine the impact of earlier versus later distribution of total daily energy intake on weight loss, and to evaluate the potential for utilizing altered energy distribution as a tool in weight loss interventions. This study is a systematic review and meta-analysis of nine clinical studies. Total number of participants was 485 (earlier distributed total energy intakes: n = 244, later distributed total energy intakes; n = 241). Results show that energy intakes with a focus on earlier distribution resulted in significantly greater weight loss when compared with similarly energy-restricted diets with individuals consuming a larger proportion of their total energy intake later in the day and into the evening. Authors conclude that earlier energy intakes may be a promising tool to be used in conjunction with other weight loss strategies such as energy restriction to enhance weight loss. However, further research is required to elucidate the additional positive impacts that earlier distributed total energy intakes may have on weight and metabolic health.
Expert Review
Conflicts of interest:
None
Take Home Message:
Implementing a dietary strategy where a higher proportion of energy is consumed earlier in the day may offer additional benefits to an energy restricted diet for weight loss, blood glucose, improve markers of insulin resistance, increase satiety and improve hunger management. Based on the findings, earlier distribution of energy intake may serve as an effective component of a weight loss protocol.
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:
Background
Chrononutrition refers to the timing and distribution of total daily energy intake across the day. It has been proposed that consuming a greater proportion of total daily energy intake earlier in the day as opposed to the evening may be beneficial for weight loss and metabolic health.
Aims
This systematic review and meta-analysis aimed to assess the impact of earlier versus later distribution of total daily energy intake on weight loss.
Results
A total of 9 randomised controlled trials involving 485 participants were included in this analysis. The study durations ranged from 5-16 weeks. All of the studies included in this analysis applied energy-restricted diets to both intervention arms. The mean percentages of energy intake in 8 of the 9 studies per meal were:
- Earlier distributed intakes: breakfast: 34% ± 16%, lunch: 38% ± 7%, dinner: 20% ± 6%.
- Later distributed intakes: breakfast: 19% ± 6%, lunch: 30% ± 10%, dinner; 40% ± 11%.
One of the studies advised percentage of energy intakes as either:
- Earlier: 70% for breakfast, morning tea and lunch and 30% for afternoon tea and dinner
- Late: 55% for breakfast, morning tea and lunch and 45% for afternoon tea and dinner.
The earlier distributed energy intake groups demonstrated significantly greater weight loss when compared with later distributed energy intake groups ( Mean Difference (MD) −1.23 kg; 95% CI −2.40, −0.06, p = 0.04;
I2 = 98%).
The earlier energy intake groups also displayed lower fasting and bedtime glucose levels (fasting: −0.83 vs. −0.27 mmol/L, p = 0.001; before sleep: −1.70 vs. −0.28 mmol/L, p = 0.009).
A random-effects model demonstrated that the earlier intake groups displayed greater reductions in LDL (MD: −0.11 mmol/L; 95% CI −0.14, −0.07, p < 0.01), fasting glucose (MD: 0.15 mmol/L, 95% CI −0.23, −0.06, p < 0.001) and HOMA-IR (MD: −0.38; 95% CI −0.64, −0.11, p = 0.005).
One study reported that earlier distribution energy intake also led to a greater reduction in medications following the intervention for type 2 diabetics (31% vs. 0%, P=0.002).
Two of the studies assessed both appetite and hunger and identified that earlier distribution of energy led to improvements in their urge to eat, preoccupation with food and cravings for sweets and fats.
Clinical practice applications:
Earlier distribution of energy intake may be beneficial for:
- Weight loss
- Improve fasting insulin, HOMA-IR, fasting glucose and HbA1c
- Reducing LDL
- Improving satiety and hunger management
- Supporting the reduction of medications for individuals with type 2 diabetes
- Improving regularity of sleep and waking times
Considerations for future research:
As the included studies only ranged from 5-16 weeks, longer duration studies would be useful to identify the effect of earlier distribution of energy intake on body weight, metabolic health and appetite over a longer period of time. There was a high degree of heterogeneity between the studies and a lack of uniformity in the distributions of energy intake across the day. Further studies with more uniformity of energy distribution would be needed to identify the optimal distribution of energy across the day to improve body weight and metabolic health.
Abstract
Consuming a greater proportion of total energy intake earlier in the day rather than in the evening is proposed to positively influence weight loss and health, potentially due to greater synchronization of human body circadian rhythms. This systematic review provides an update on existing evidence regarding earlier distributed eating patterns in weight loss interventions. Using a robust search strategy in five electronic databases, nine randomized controlled trials investigating the impact of energy intake distribution on weight loss were identified. Following critical appraisal, a random-effects meta-analyses found that, in the context of an energy-reduced diet, distributing energy intake with a focus on earlier intake resulted in significantly greater weight loss (-1.23 kg; 95% CI 2.40, -0.06, p = 0.04). Improvements in HOMA-IR, fasting glucose, and LDL cholesterol were also seen. The current study provides a timely update on the evidence linking distribution of total daily energy intake and health, showing that a focus on earlier intakes can result in greater short-term weight loss compared with later intakes. Future studies are needed to elucidate the impact that earlier intakes may have on weight management and metabolic health.
3.
Effects of Diet on 10-Year Atherosclerotic Cardiovascular Disease Risk (from the DASH Trial).
Jeong, SY, Wee, CC, Kovell, LC, Plante, TB, Miller, ER, Appel, LJ, Mukamal, KJ, Juraschek, SP
The American journal of cardiology. 2023;187:10-17
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Determining the 10-year risk of heart disease can be used as tool to determine appropriate treatment plans. This study of 459 adults aged 22-75 years with obesity aimed to compare the effects on the 10-year risk for the development heart disease of an 8-week dietary approaches to stop hypertension (DASH) diet, with the standard American diet (AD) and a diet high in fruits and vegetables (F/V). The results showed that the DASH diet significantly improved risk factors such as systolic blood pressure and total cholesterol. However, the F/V diet had an improvement in good cholesterol, which the DASH diet did not. This equated to a similar 10% reduction in the 10-year heart disease risk compared to the AD. It was concluded that compared to a typical AD, DASH and F/V diets reduced the risk for heart disease over a 10-year period. However, the actual risk reduction was only small and individuals with obesity may need to reduce their risk further with other therapies. This study could be used by healthcare professionals to recommend a DASH diet or a diet high in fruits and vegetables to reduce the long-term risk for heart disease alongside other proven therapies or methods to reduce risk.
Expert Review
Conflicts of interest:
None
Take Home Message:
- DASH and F/V diets may be of benefit to obese individuals to decrease their risk for ASCVD
- The DASH diet did reduce HDL cholesterol and recommendations should be made to limit this effect (e.g. exercise and more fruit and vegetables in the diet).
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
This study aimed to determine the effect of the Dietary Approaches to Stop Hypertension (DASH) diet compared to a standard American diet (AD) and a diet emphasising fruits and vegetables (F/V) on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) and how adopting these diets affect specific risk factors (e.g systolic blood pressure (SBP), diastolic blood pressure (DBP) and blood lipids).
Methods
- Secondary analysis from the DASH trial which ran for 8 weeks in 459 adults aged 22-75 years with obesity
- All meals were provided and dietary intake was adjusted to prevent weight loss
- The primary outcome was an absolute and relative difference in 10-year ASCVD risk from baseline.
Participants were randomised to one of three diets:
1) DASH diet
2) F/V diet, similar to AD but with more fruits and vegetables and higher potassium and magnesium
3) Standard AD.
Results
- DASH significantly lowered SBP, total cholesterol, and HDL cholesterol compared to F/V (absolute difference SBP: -2.8, (95% confidence interval [CI]-4.5, -1.2), total cholesterol: 9.3 (-14.7, 3.9), and HDL cholesterol: -3.5 (-5.0, -2.1) P=<0.05 for all)
- DASH significantly lowered SBP, total cholesterol, and HDL cholesterol compared to AD (absolute difference SBP: -5.3 (-7.0, -3.7), total cholesterol: -13.1 (-18.5, -7.7), and HDL cholesterol: -3.8 (-5.2, -2.4) P=<0.05 for all)
- Compared to AD, DASH and F/V diets reduced 10-year ASCVD relative risk by -10.3%
( −14.4 to −5.9) and −9.9% ( −14.0 to −5.5) respectively
- This translated into low actual risk reductions of -0.21% for the F/V diet and -0.17% for the DASH diet
- Although DASH improved SBP, and total cholesterol compared to F/V, no differences in ASCVD risk between DASH and F/V were apparent. This was attributable to the detrimental effect of the DASH diet on HDL cholesterol, which was not seen in the F/V diet
- The effects of the DASH diet were more pronounced in black participants and in women.
Conclusion
Compared to the AD, DASH and F/V reduced 10-year ASCVD risk by approximately 10% over 8-weeks. The DASH diet was more effective for women and black adults.
Clinical practice applications:
- DASH and F/V diets decrease risk factors and an individual’s risk of ASCVD, and should be encouraged in individuals with obesity, especially women and black adults
- However, these diets do still leave obese individuals at risk for ASCVD.
Considerations for future research:
- Research on these diets in combination with weight loss regimes may give more pronounced results
- It may also be interesting to understand the mechanisms behind why the DASH diet reduces HDL cholesterol.
Abstract
Although modern risk estimators, such as the American College of Cardiology/American Heart Association Pooled Cohort Equation, play a central role in the decisions of patients to start pharmacologic therapy to prevent atherosclerotic cardiovascular disease (ASCVD), there is limited evidence to inform expectations for 10-year ASCVD risk reduction from established lifestyle interventions. Using data from the original DASH (Dietary Approaches to Stop Hypertension) trial, we determined the effects of adopting the DASH diet on 10-year ASCVD risk compared with adopting a control or a fruits and vegetables (F/V) diet. The DASH trial included 459 adults aged 22 to 75 years without CVD and not taking antihypertensive or diabetes mellitus medications, who were randomized to controlled feeding of a control diet, an F/V diet, or the DASH diet for 8 weeks. We determined 10-year ASCVD risk with the American College of Cardiology/American Heart Association Pooled Cohort Equation based on blood pressure and lipids measured before and after the 8-week intervention. Compared with the control diet, the DASH and F/V diets changed 10-year ASCVD risk by -10.3% (95% confidence interval [CI] -14.4 to -5.9) and -9.9% (95% CI -14.0 to -5.5) respectively; these effects were more pronounced in women and Black adults. There was no difference between the DASH and F/V diets (-0.4%, 95% CI -6.9 to 6.5). ASCVD reductions attributable to the difference in systolic blood pressure alone were -14.6% (-17.3 to -11.7) with the DASH diet and -7.9% (-10.9 to -4.8) with the F/V diet, a net relative advantage of 7.2% greater relative reduction from DASH compared with F/V. This was offset by the effects on high-density lipoprotein of the DASH diet, which increased 10-year ASCVD by 8.8% (5.5 to 12.3) compared with the more neutral effect of the F/V diet of -1.9% (-5.0 to 1.2). In conclusion, compared with a typical American diet, the DASH and F/V diets reduced 10-year ASCVD risk scores by about 10% over 8 weeks. These findings are informative for counseling patients on both choices of diet and expectations for 10-year ASCVD risk reduction.
4.
Longitudinal association of dietary carbohydrate quality with visceral fat deposition and other adiposity indicators.
Zamanillo-Campos, R, Chaplin, A, Romaguera, D, Abete, I, Salas-Salvadó, J, Martín, V, Estruch, R, Vidal, J, Ruiz-Canela, M, Babio, N, et al
Clinical nutrition (Edinburgh, Scotland). 2022;41(10):2264-2274
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Abdominal obesity, measured by waist circumference, a proxy of visceral fat, is increasing at an even greater rate than overall obesity alone. Diet plays a key role in body fat accumulation; however, recent evidence also indicates that, beyond quantity, the quality of certain nutrients may have an independent effect. The aim of this study was to determine the dynamic association between changes in overall dietary carbohydrate quality and changes in objectively measured visceral and overall adiposity distribution This study is a prospective cohort study based on data collected during the first year of the PREDIMED-Plus (PREvencion con DIeta MEDiterranea Plus) randomised controlled trial. In the PREDIMED-Plus trial, a total of 6874 people were randomly allocated in a 1:1 ratio to either the intervention or control group. Results show that a carbohydrate quality index increase was associated with a decrease in regional and overall adiposity. The observed associations were mostly driven by fibre and the wholegrains/total grains ratio. Authors conclude that the promotion of fibre-rich foods, including fruits, vegetables, legumes and nuts, and the substitution of refined grains by wholegrains, may be important dietary recommendations to adopt in clinical practice to promote a healthier body composition.
Expert Review
Conflicts of interest:
None
Take Home Message:
This prospective cohort of older adults with overweight/obesity and MetS, found that improvements in dietary carbohydrate quality over one year was associated with positive changes in visceral and overall fat deposition, largely due to dietary fibre and the wholegrain/total grain ratio.
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:
Background
Obesity prevalence is increasing worldwide and is associated with a range of metabolic and cardiovascular diseases. Excess visceral fat appears with increasing age but also with unhealthy dietary patterns and lifestyle behaviours, and it contributes to chronic diseases, particularly type 2 diabetes (T2D), insulin resistance, metabolic syndrome (MetS), and cardiovascular diseases (CVD).
Aim
This study determined the association between changes in overall dietary carbohydrate quality and changes in objectively-measured visceral and overall adiposity distribution. Three repeated measurements of diet and adiposity were conducted throughout a 1-year follow-up, using a dual-energy X-ray absorptiometry (DXA) scans for body composition assessment.
The study compared an intensive weight-loss (intervention group) using an energy-reduced Mediterranean Diet (MedDiet), with physical activity (PA), and behavioural support on the prevention of CVD events, compared to usual care and dietary counselling only.
This prospective cohort study analysed a subgroup of 1476 participants (men aged 55-75 years and women aged 60-75 years) enrolled in the PREDIMED-Plus randomized controlled trial. Participants were overweight or obese (BMI>27 kg/m2 and <40 kg/m2) with no previous cardiovascular events and at least three characteristics of metabolic syndrome (MetS): hypertension, hyper-triglyceridemia, lower high-density lipoprotein (HDL) cholesterol, hyperglycemia, or central obesity.
Dietary intake was measured at baseline, 6- and 12-months using a Spanish version of the validated 143-item semi-quantitative food-frequency questionnaire, via face-to-face interviews by trained dietitian-nutritionists. Carbohydrate quality index (CQI) was calculated using four criteria: total dietary fibre, glycemic index, wholegrain/total grain carbohydrate ratio, and solid/total carbohydrate ratio.
Results
Improvements in body composition and lifestyle factors were observed compared to baseline data (both study arms combined) (p < 0.05 for all). A higher Carbohydrate Quality Index CQI (p = 0.024) was observed at both the 6 and 12 month follow-up.
A 3-point increment in CQI over 12-month follow-up was associated with a decrease in visceral fat (β 0.067 z-score, 95% CI -0.088 to -0.046, p<0.001), android-to-gynoid fat ratio* (β -0.038, 95% CI -0.059 to -0.017, p<0.001) (*calculated by dividing the fat mass (g) from the specific regions), and total fat (β -0.064, 95% CI -0.080 to -0.047, p<0.001).
Fibre intake and the ratio of whole grain/total grain showed the strongest inverse associations with all adiposity indicators. Statistically significant differences were observed over time in all CQI components. The most relevant changes were the increase in consumption of carbohydrates from whole-grains and a decrease in refined grains, and an increase in dietary fibre intake. After evaluating each CQI component separately, the study found that fibre intake and the ratio of whole grain/total grain presented the strongest and statistically significant negative associations with all adiposity indicators (all p-values <0.01).
Limitations
Due to the observational nature of the study, causality cannot be inferred. The study population is based on older people with overweight/obesity and MetS from a Mediterranean area, which can limit the generalisability of findings to the general population.
The use of self-reported dietary data is subject to measurement error, where self-reports may be affected by a tendency to respond in a manner to avoid criticism or judgement and to seek social approval.
Clinical practice applications:
Evidence has shown that the quality of dietary carbohydrates, rather than the quantity, may have a greater impact on health and overall mortality.
While visceral fat constitutes only a small proportion of total fat, the available evidence indicates that it plays an important role in certain chronic diseases, such as T2D, MetS, CVD and cancer.
Findings from this study suggest a better CQI via the manipulation of carbohydrate quality may be associated with a decrease in visceral fat, which are independent of changes in total body fat.
Considerations for future research:
Future strategies to decrease visceral fat are warranted.
Robust reference ranges are needed for the interpretation of visceral fat in clinical practice and research settings.
Abstract
BACKGROUND & AIMS The quality of dietary carbohydrates rather than total carbohydrate intake may determine the accumulation of visceral fat; however, to date, few studies have examined the impact of diet on adiposity using specific imaging techniques. Thus, the aim of this prospective study was to investigate the association between concurrent changes in carbohydrate quality index (CQI) and objectively-quantified adiposity distribution over a year. METHODS We analyzed a cohort of 1476 participants aged 55-75 years with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus randomized controlled trial. Dietary intake information was obtained at baseline, 6- and 12-months from a validated 143-item semi-quantitative food-frequency questionnaire, and CQI (range: 4 to 20) was calculated based on four dietary criteria: total dietary fibre, glycemic index, wholegrain/total grain carbohydrate ratio, and solid/total carbohydrate ratio. Overall and regional adiposity (total body fat, visceral fat and android-to-gynoid fat ratio) was quantified using dual-energy X-ray absorptiometry at all three time points. Multiple adjusted linear mixed-effects models were used to assess associations between concurrent changes in repeatedly measured CQI and adiposity over time. RESULTS After controlling for potential confounding factors, a 3-point increment in CQI over 12-month follow-up was associated with a decrease in visceral fat (β -0.067 z-score, 95% CI -0.088; -0.046, p < 0.001), android-to-gynoid fat ratio (-0.038, -0.059; -0.017, p < 0.001), and total fat (-0.064, -0.080; -0.047, p < 0.001). Fibre intake and the ratio of wholegrain/total grain showed the strongest inverse associations with all adiposity indicators. CONCLUSIONS In this prospective cohort of older adults with overweight/obesity and MetS, we found that improvements in dietary carbohydrate quality over a year were associated with concurrent favorable changes in visceral and overall fat deposition. These associations were mostly driven by dietary fibre and the wholegrain/total grain ratio. TRIAL REGISTRATION The trial was registered at the International Standard Randomized. CONTROLLED TRIAL (ISRCTN http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.
5.
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.