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Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial.
Katayoshi, T, Uehata, S, Nakashima, N, Nakajo, T, Kitajima, N, Kageyama, M, Tsuji-Naito, K
Scientific reports. 2023;13(1):2786
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Nicotinamide adenine dinucleotide (NAD+) is a coenzyme that plays a crucial role in energy metabolism and different biological processes. Sirtuins (SIRT1) are NAD+-dependent deacetylases, an enzyme that plays a key role in enhancing metabolic efficiency. Nicotinamide mononucleotide (NMN) is a precursor to NAD+. NMN supplementation may help to reduce the risk of developing metabolic diseases and cardiovascular diseases. This randomised, double-blinded, and placebo-controlled, parallel trial investigated the effects of 12 weeks of 125 mg NMN supplementation on metabolic health parameters, including CVD risk factors, blood NAD+ metabolites level, and SIRT1 expression in middle-aged men and women. Serum nicotinamide was significantly higher and arterial stiffness was lower in the NMN test group of middle-aged men and women after 12 weeks of NMN supplementation. The results of the study indicate that the administration of 250mg of nicotinamide mononucleotide (NMN) daily for an extended period is considered safe and well-tolerated. Healthcare professionals can use this finding to understand the significant implications of the use of NMN as a potential therapeutic agent in individuals seeking to improve their metabolic and cardiovascular health. Further robust studies are required to evaluate the effects of NMN supplementation due to the limitations and high baseline variability between the participants of this study.
Expert Review
Conflicts of interest:
None
Take Home Message:
- As we age, NAM levels decline, which could have a negative effect on cardiovascular health.
- Middle-aged adults may like to consider NMN supplementation to improve NAM metabolism and arterial stiffness.
- However, without data on CVD events, it is difficult to determine actual risk reductions.
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
- Nicotinamide adenine dinucleotide (NAD+) is a coenzyme involved in metabolism. When we age, NAD+ levels decline resulting in poorer metabolism and age-related disease such as cardiovascular disease (CVD). Nicotinamide mononucleotide (NMN) is a precursor in the biosynthesis of NAD+.
- This double-blind, randomised control trial aimed to determine the effect of supplementing NMN on NAD+ levels, CVD risk factors and sirtuin 1 (SIRT1) expression, which relies on NAD+ for adequate functioning.
Methods
- 36 healthy male and female individuals aged between 40-65 years of age were assigned to either NMN (125mg/day) or placebo for 12 weeks.
- One capsule was taken twice per day after meals.
- Serum nicotinamide (NAM), NAD+, NMN, advanced glycation end products (AGES), 8-hydroxydeoxyguanosine (8-OHdG) and SIRT1 mRNA expression were measured.
- The condition of blood vessels (arterial stiffness) was also assessed using the ankle brachial index (ABI).
- In a sub-analysis, individuals with hypertension, above average body mass index (BMI), or blood glucose level were also assessed for blood vessel condition using the ABI.
Results
- The results showed that from baseline serum NAM decreased in the placebo group (P=0.014), whereas it increased in the NMN group (P=0.006). This resulted in an increase in the NMN group compared to placebo (P=0.037).
- Interestingly serum NAM was lower in the NMN group compared to placebo at baseline (P=0.001).
- There was no statistically significant difference in ABI with NMN supplementation.
- Amongst those with hypertension there was also no change in ABI. However, those with high BMI or blood glucose, there was an improvement in vascular condition compared to placebo (P=<0.007 and P=0.019 respectively).
- 8-OHdG, SIRT1 mRNA and AGEs remained unchanged by NMN supplementation
Conclusion
- NMN supplementation enhanced NAD+ metabolism in middle-aged adults.
- It also relieved arterial stiffness and reduced CVD risk factors.
Clinical practice applications:
- Apparently healthy middle-aged adults who would like to activate NAD metabolism and decrease their risk for CVD, should consider 12-week supplementation with NMN (125mg/day).
- ABI should be monitored to ensure desired effects.
- It is unclear as to the effects of NMN supplementation after 12-weeks.
Considerations for future research:
- Future research should consider longer supplementation duration and/or adding in a follow-up period to determine duration of effect.
- Different supplemental doses should also be researched to determine an optimal dose.
Abstract
Many animal studies have shown that oral administration of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) prevents the reduction of NAD+ levels in organs and tissues, helping alleviate aging-related diseases. However, there are very few clinical reports of NMN supplementation in humans. Thus, this study aimed to investigate the influence of a 12-week NMN oral supplementation on biochemical and metabolic health parameters. A 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 36 healthy middle-aged participants received one capsule of either 125 mg NMN or placebo twice a day. Among the NAD+ metabolites, the levels of nicotinamide in the serum were significantly higher in the NMN intake group than in the placebo group. Pulse wave velocity values indicating arterial stiffness tended to decrease in the NMN intake group. However, no significant difference was found between the two groups. Long-term NMN supplementation at 250 mg/day was well tolerated and did not cause adverse events. NMN safely and effectively elevated NAD+ metabolism in healthy middle-aged adults. Additionally, NMN supplementation showed potential in alleviating arterial stiffness.
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Impact of the COVID-19 pandemic on the glycemic control, eating habits, and body compositions of people with diabetes mellitus: A retrospective longitudinal observational study.
Sawada, M, Ohkuma, K, Aihara, M, Doi, S, Sekine, R, Kaneko, T, Iimuro, S, Ichi, I, Usami, S, Ohe, K, et al
Journal of diabetes investigation. 2023;14(2):321-328
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Several systematic reviews and meta-analyses conducted to evaluate the prognosis of coronavirus disease-2019 (COVID-19) in people with diabetes mellitus have reported an approximately two- to three-fold higher risk of mortality from COVID-19 in people with diabetes mellitus compared with those without diabetes mellitus. The aim of this study was to investigate the impact of the COVID-19 pandemic and the state of emergency on the glycaemic control, eating habits, and body composition of people with diabetes mellitus. This study is a retrospective, longitudinal observational study in outpatients with diabetes mellitus. A total of 408 participants were included in this study, including 239 men (58.6%) and 169 women (41.4%). People with type 2 diabetes mellitus were predominant in this study (96.8%). Results show that: - there was a significant increase of the haemoglobin A1c level in people with diabetes mellitus during the COVID-19 pandemic. - there was an increase in the changes in body weight and percent fat (increased) and skeletal muscle masses (decreased). Authors conclude that the COVID-19 pandemic caused a negative impact on the glycaemic control and body composition in people with diabetes mellitus. Furthermore, the increase of body weight and fat mass and the decrease of the skeletal muscle mass during the pandemic were associated with poor glycaemic control, independent of the age and sex, in people with diabetes mellitus.
Abstract
AIMS/INTRODUCTION To evaluate the impact of the COVID-19 pandemic on the glycemic control, eating habits, and body composition of people with diabetes mellitus; to identify the determinants of worsening glycemic control in people with diabetes mellitus. MATERIALS AND METHODS This retrospective, longitudinal observational study was performed in outpatients with diabetes mellitus who visited our hospital between April 2019 and March 2020 (pre-COVID-19 period) and continued for follow up from April 2020 to March 2021 (COVID-19 period). We compared the glycemic control, nutritional intakes, and body composition of people with diabetes mellitus between the two periods. The changes in the HbA1c values (ΔHbA1c) and other study variables were compared between the two periods. Logistic regression analysis was performed to identify the factors associated with the increase of HbA1c levels. RESULTS A significant increase of HbA1c was observed during the COVID-19 period. The percent fat mass (FM) also increased, while the percent skeletal muscle mass (SMM) decreased during the COVID-19 period. After adjustments for age and sex, the ΔBMI (OR:2.33), ΔFM (OR:1.45), and ΔSMM (OR:0.51) were identified as being associated with elevated levels of HbA1c. CONCLUSIONS The COVID-19 pandemic had a negative impact on the glycemic control and body composition of people with diabetes mellitus. The increased body weight and FM and decreased SMM observed during the pandemic were associated with poor glycemic control in people with diabetes mellitus.
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Acute Effects of Dietary Nitrate on Central Pressure and Endothelial Function in Hypertensive Patients: A Randomized, Placebo-Controlled Crossover Study.
Mattos, S, Cunha, MR, Marques, BC, D El-Rei, J, Baião, DDS, Paschoalin, VMF, Oigman, W, Neves, MF, Medeiros, F
Arquivos brasileiros de cardiologia. 2023;120(1):e20220209
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Eating habits influence several mechanisms involved with cardiovascular risk factors. The inorganic nitrate (NO3‾) content in root vegetables can provide a physiological substrate for the reduction to nitrite (NO2‾), nitric oxide and other metabolic products. The aim of this study was to evaluate the acute effects of dietary NO3‾ intake on blood pressure (BP) and endothelial function in treated hypertensive patients. This study was a randomised, crossover, placebo-controlled study which enrolled thirty-seven hypertensive patients aged between 40 and 70 years, of both genders, in regular use of antihypertensive drugs. Each participant was randomised to the crossover interventions; beetroot juice (BRJ) [rich in inorganic NO3‾] or water. Results show that after a single intake of inorganic NO3‾ there was an attenuation in the peripheral and central BP levels, reduction of ejection duration [the period in the cardiac cycle when the semilunar valves are open and blood is being ejected from the ventricles into the arterial system], increase in subendocardial viability ratio [an arterial stiffness parameter correlated with coronary flow reserve] and improvement of vascular function associated with elevated serum NO3‾ and NO2‾. Authors conclude that the intake of BRJ resulted in acute benefits on vascular parameters in hypertensive individuals, leading to greater subendocardial viability, higher performance in myocardial contraction and improvement in endothelial function.
Abstract
BACKGROUND The diet's inorganic nitrate (NO3-) may provide a physiological substrate for reducing nitrate (NO2-) to NO independent of the endothelium. Studies suggest that inorganic NO3- has beneficial effects on cardiovascular health. OBJECTIVE This study evaluated the acute effects of 500 mL nitrate-rich beetroot juice (BRJ; containing 11.5mmol NO3-) on blood pressure and endothelial function in treated hypertensive patients. METHODS A randomized, placebo-controlled, crossover study was conducted in treated hypertensive patients (n=37; women=62%) who underwent clinical and nutritional evaluation and assessment of central hemodynamic parameters and microvascular reactivity. The significance level was p<0.05. RESULTS The mean age was 59±7 years, and mean systolic and diastolic blood pressures were 142±10/83±9mmHg. There was a significant increase in the subendocardial viability ratio (SEVR; 149±25 vs. 165±30%, p<0.001) and reduction in ejection duration (ED; 37±4 vs. 34±4%, p<0.001) in the beetroot phase but no significant SEVR difference in the control phase. The % increase in perfusion (155 vs. 159 %, p=0.042) was significantly increased in the beetroot phase, which was not observed in the control phase. In the beetroot phase, the change in SEVR showed a significant correlation with the change in the area under the curve of post-occlusive reactive hyperemia (AUC-PORH) (r=0.45, p=0.012). The change in ED showed a significant correlation with the post-intervention perfusion peak (r=-0.37, p=0.031) and AUC-PORH (r=-0.36, p=0.046). CONCLUSIONS The acute ingestion of BRJ by hypertensive patients resulted in an improvement of endothelial function, which was associated with higher subendocardial viability and performance in myocardial contraction. FUNDAMENTO O nitrato inorgânico (NO3–) da dieta pode fornecer substrato fisiológico para reduzir o nitrito (NO2–) a óxido nítrico (NO) independente do endotélio. Estudos sugerem que o NO3– inorgânico tem efeitos benéficos na saúde cardiovascular. OBJETIVOS Este estudo avaliou os efeitos agudos de 500 mL de suco de beterraba rico em nitrato (SB; contendo 11,5mmol NO3–) na pressão arterial e na função endotelial em pacientes hipertensos tratados. MÉTODOS Estudo cruzado, randomizado, controlado por placebo foi realizado em pacientes hipertensos tratados (n=37; mulheres=62%) que foram submetidos à avaliação clínica e nutricional, avaliação dos parâmetros hemodinâmicos centrais e reatividade microvascular. O nível de significância foi p<0,05. RESULTADOS A média de idade foi 59±7 anos e das pressões sistólica e diastólica foi de 142±10/83±9 mmHg. Houve aumento significativo na taxa de viabilidade subendocárdica (RVSE; 149±25 vs. 165±30%, p<0,001) e redução na duração da ejeção (DE; 37±4 vs. 34±4%, p<0,001) na fase beterraba, mas nenhuma diferença significativa de RVSE na fase controle. O % de aumento na perfusão (155 vs. 159%, p=0,042) cresceu significativamente na fase beterraba, o que não foi observado na fase controle. Na fase beterraba, a alteração da RVSE apresentou correlação significativa com a alteração da área sob a curva de hiperemia reativa pós-oclusiva (ASC-HRPO) (r=0,45, p=0,012). A mudança na DE mostrou uma correlação significativa com pico de perfusão pós-intervenção (r=-0,37, p=0,031) e ASC-HRPO (r=-0,36, p=0,046). CONCLUSÃO: A ingestão aguda de SB por pacientes hipertensos resultou em melhora da função endotelial, que foi associada à maior viabilidade subendocárdica e desempenho na contração miocárdica. BACKGROUND The diet’s inorganic nitrate (NO3–) may provide a physiological substrate for reducing nitrate (NO2–) to NO independent of the endothelium. Studies suggest that inorganic NO3–has beneficial effects on cardiovascular health. OBJECTIVE This study evaluated the acute effects of 500 mL nitrate-rich beetroot juice (BRJ; containing 11.5mmol NO3–) on blood pressure and endothelial function in treated hypertensive patients. METHODS A randomized, placebo-controlled, crossover study was conducted in treated hypertensive patients (n=37; women=62%) who underwent clinical and nutritional evaluation and assessment of central hemodynamic parameters and microvascular reactivity. The significance level was p<0.05. RESULTS The mean age was 59±7 years, and mean systolic and diastolic blood pressures were 142±10/83±9mmHg. There was a significant increase in the subendocardial viability ratio (SEVR; 149±25 vs. 165±30%, p<0.001) and reduction in ejection duration (ED; 37±4 vs. 34±4%, p<0.001) in the beetroot phase but no significant SEVR difference in the control phase. The % increase in perfusion (155 vs. 159 %, p=0.042) was significantly increased in the beetroot phase, which was not observed in the control phase. In the beetroot phase, the change in SEVR showed a significant correlation with the change in the area under the curve of post-occlusive reactive hyperemia (AUC-PORH) (r=0.45, p=0.012). The change in ED showed a significant correlation with the post-intervention perfusion peak (r=-0.37, p=0.031) and AUC-PORH (r=-0.36, p=0.046). CONCLUSIONS The acute ingestion of BRJ by hypertensive patients resulted in an improvement of endothelial function, which was associated with higher subendocardial viability and performance in myocardial contraction.
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Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials.
Wang, T, Zhang, X, Zhou, N, Shen, Y, Li, B, Chen, BE, Li, X
Journal of the American Heart Association. 2023;12(11):e029512
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Dyslipidaemia is considered to be a risk factor for cardiovascular disease (CVD) and the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to confer benefits for both dyslipidaemia and CVD, although results from clinical trials and meta-analyses (studies pooling data from smaller studies to increase statistical power) are mixed. The aim of this meta-analysis, using a particular statistical method, was to evaluate whether dose-response relationships may be non-linear. This meta-analysis included 90 randomised controlled trials with 72,598 participants overall. Lipids evaluated were triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and non-HDL cholesterol. A near linear relationship was seen between intake of combined EPA and DHA and a decrease in TG and non-HDL, both overall and for the subgroups of patients with and without hyperlipidaemia and overweight. For LDL and HDL, J-shaped relationships were seen, with an increase followed by a decrease with increasing EPA + DHA intake, both overall and in the subgroups with and without hyperlipidaemia. The authors also pooled data from studies which used the red blood cell omega index (a measure of omega-3 status) and found that with increasing omega-3 status, TG and non-HDL declined whilst HDL increased in a near linear fashion, whilst there was still a J-shaped curve for LDL. The authors consider that a medium dose of EPA + DHA may be needed for the management of dyslipidaemia, and a high dose for people at high risk of developing CVD.
Abstract
Background Previous results provide supportive but not conclusive evidence for the use of omega-3 fatty acids to reduce blood lipids and prevent events of atherosclerotic cardiovascular disease, but the strength and shape of dose-response relationships remain elusive. Methods and Results This study included 90 randomized controlled trials, reported an overall sample size of 72 598 participants, and examined the association between omega-3 fatty acid (docosahexaenoic acid, eicosapentaenoic acid, or both) intake and blood lipid changes. Random-effects 1-stage cubic spline regression models were used to study the mean dose-response association between daily omega-3 fatty acid intake and changes in blood lipids. Nonlinear associations were found in general and in most subgroups, depicted as J-shaped dose-response curves for low-/high-density lipoprotein cholesterol. However, we found evidence of an approximately linear dose-response relationship for triglyceride and non-high-density lipoprotein cholesterol among the general population and more evidently in populations with hyperlipidemia and overweight/obesity who were given medium to high doses (>2 g/d). Conclusions This dose-response meta-analysis demonstrates that combined intake of omega-3 fatty acids near linearly lowers triglyceride and non-high-density lipoprotein cholesterol. Triglyceride-lowering effects might provide supportive evidence for omega-3 fatty acid intake to prevent cardiovascular events.
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Gut microbiome modulates the effects of a personalised postprandial-targeting (PPT) diet on cardiometabolic markers: a diet intervention in pre-diabetes.
Ben-Yacov, O, Godneva, A, Rein, M, Shilo, S, Lotan-Pompan, M, Weinberger, A, Segal, E
Gut. 2023;72(8):1486-1496
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Diet is a major contributor to cardiometabolic health and plays a fundamental role in the prevention, management and even reversal of many chronic diseases. The gut microbiota has a central role in human health and disease. Specifically, its role in cardiometabolic health has been studied extensively in recent years. The aim of this study was to evaluate the interplay between dietary modifications, microbiome composition and cardiometabolic health outcomes. This study was a randomised controlled trial of a 6-month dietary intervention comparing a personalised postprandial-targeting (PPT) diet versus Mediterranean (MED) diet in 200 adults with pre-diabetes. Results showed that: - PPT intervention induced greater changes in multiple dietary features compared with MED intervention. - PPT intervention increased microbiome diversity and richness and exerted specific microbiome species changes that associate with clinical outcomes. - Changes in specific gut microbiome species partially mediated the effects of dietary modifications on clinical outcomes. Authors conclude that the PPT diet prompted greater changes in gut microbiota composition, consistent with overall greater dietary modifications, as compared with the MED intervention.
Abstract
OBJECTIVE To explore the interplay between dietary modifications, microbiome composition and host metabolic responses in a dietary intervention setting of a personalised postprandial-targeting (PPT) diet versus a Mediterranean (MED) diet in pre-diabetes. DESIGN In a 6-month dietary intervention, adults with pre-diabetes were randomly assigned to follow an MED or PPT diet (based on a machine-learning algorithm for predicting postprandial glucose responses). Data collected at baseline and 6 months from 200 participants who completed the intervention included: dietary data from self-recorded logging using a smartphone application, gut microbiome data from shotgun metagenomics sequencing of faecal samples, and clinical data from continuous glucose monitoring, blood biomarkers and anthropometrics. RESULTS PPT diet induced more prominent changes to the gut microbiome composition, compared with MED diet, consistent with overall greater dietary modifications observed. Particularly, microbiome alpha-diversity increased significantly in PPT (p=0.007) but not in MED arm (p=0.18). Post hoc analysis of changes in multiple dietary features, including food-categories, nutrients and PPT-adherence score across the cohort, demonstrated significant associations between specific dietary changes and species-level changes in microbiome composition. Furthermore, using causal mediation analysis we detect nine microbial species that partially mediate the association between specific dietary changes and clinical outcomes, including three species (from Bacteroidales, Lachnospiraceae, Oscillospirales orders) that mediate the association between PPT-adherence score and clinical outcomes of hemoglobin A1c (HbA1c), high-density lipoprotein cholesterol (HDL-C) and triglycerides. Finally, using machine-learning models trained on dietary changes and baseline clinical data, we predict personalised metabolic responses to dietary modifications and assess features importance for clinical improvement in cardiometabolic markers of blood lipids, glycaemic control and body weight. CONCLUSIONS Our findings support the role of gut microbiome in modulating the effects of dietary modifications on cardiometabolic outcomes, and advance the concept of precision nutrition strategies for reducing comorbidities in pre-diabetes. TRIAL REGISTRATION NUMBER NCT03222791.
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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.
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Inflammation moderates the effects of lifestyle modification on neurocognition among individuals with resistant hypertension.
Avorgbedor, F, Blumenthal, JA, Hinderliter, A, Ingle, K, Lin, PH, Craighead, L, Tyson, C, Kraus, W, Sherwood, A, Smith, PJ
Journal of clinical hypertension (Greenwich, Conn.). 2023;25(1):106-110
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Hypertension is one of the primary causes of cardiovascular disease, stroke, Alzheimer’s Disease, and Alzheimer’s Disease and related dementias (AD/ADRD). Among individuals with hypertension, those with resistant hypertension (RH) appear to have the greatest risk of cerebrovascular disease and associated cognitive impairment. The aim of this study was to investigate the potential influence of individual differences in pre-treatment inflammatory profiles on changes in cognition following lifestyle modification among RH participants in the TRIUMPH clinical trial. This study is a report based on the TRIUMPH study which was a randomised clinical trial. One hundred forty patients with RH were randomised with 2:1 allocation to either a 4-month Centre-based Lifestyle intervention or Standardized Education and Physician Advice. Results show that basal levels of elevated peripheral inflammation may represent an intermediate phenotype of risk for cognitive decline. In fact, individuals with higher levels of c-reactive protein at baseline demonstrated greater improvements in Executive Function/Learning following participation in an intensive lifestyle intervention. Authors conclude that their findings may help inform targeted treatments to reduce ADRD among middle-aged and older adults with cardiovascular disease risk factors.
Abstract
Individuals with resistant hypertension (RH) have the greatest risk of cerebrovascular disease and cognitive impairment among individuals with hypertension. Elevated levels of pro-inflammatory cytokines may represent a critical yet unexamined factor influencing the impact of healthy lifestyle changes on cognitive function. We explored the influence of inflammation on changes in cognition following lifestyle modification among individuals with RH participating in the TRIUMPH clinical trial. One hundred forty participants with RH completed a battery of neurocognitive tests along with the inflammatory marker C-reactive protein (hsCRP) and were subsequently randomized to an intensive 4-month lifestyle modification intervention or to education and physician advice control. Results indicated that the effects of lifestyle modification on Executive Function and Learning were moderated by pre-intervention hsCRP levels (P = .049), with treatment efficacy increasing across levels of baseline inflammation levels (low: d = 0.12; mild: d = 0.43; moderate: d = 0.81). We conclude that inflammatory profiles may help identify individuals more likely to improve executive functioning resulting from lifestyle modification.
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Inverse Association Between Serum 25-Hydroxyvitamin D and Nonalcoholic Fatty Liver Disease.
Yuan, S, Larsson, SC
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023;21(2):398-405.e4
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The prevalence of non-alcoholic fatty liver disease (NAFLD) is projected to increase due to the obesity epidemic, rise in diabetes prevalence, and other factors. An inverse association between serum 25-hydroxyvitamin D [S-25(OH)D], a clinical marker of vitamin D status, and NAFLD has been observed in several cross-sectional and case-control studies. The aim of this study was to determine the association between S-25(OH)D and NAFLD. This study is a 2-sample Mendelian randomisation study based on summary-level data of genome-wide association analyses on S-25(OH)D levels, NAFLD, and liver enzymes. Results show an inverse genetic correlation of S-25(OH)D with NAFLD and certain liver enzymes and an inverse association of genetically predicted S-25(OH)D with risk of NAFLD in European individuals. Authors conclude that vitamin D may play a role in NAFLD prevention. However, further studies are needed in order to confirm the causal effect of NAFLD on lowering S-25(OH)D levels.
Abstract
BACKGROUND & AIMS Serum 25-hydroxyvitamin D [S-25(OH)D] and nonalcoholic fatty liver disease (NAFLD) are correlated in many observational studies, whereas the causality of this association is uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to determine the association between S-25(OH)D and NAFLD. METHODS Seven and 6 independent genetic variants associated with S-25(OH)D and NAFLD at the genome-wide-significance level, respectively, were selected as instrumental variables. Summary-level data for S-25(OH)D were obtained from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium including 79,366 individuals. Summary-level data for NAFLD were available from a genome-wide association meta-analysis (1483 cases and 17,781 controls), the FinnGen consortium (894 cases and 217,898 controls), and the UK Biobank study (275 cases and 360,919 controls). Summary-level data for 4 liver enzymes were obtained from the UK Biobank. RESULTS There were genetic correlations of S-25(OH)D with NAFLD and certain liver enzymes. Genetically predicted higher levels of S-25(OH)D were consistently associated with a decreased risk of NAFLD in the 3 sources. For a 1-SD increase in genetically predicted S-25(OH)D levels, the combined odds ratio of NAFLD was 0.78 (95% confidence interval [CI], 0.69 to 0.89). Genetically predicted higher levels of S-25(OH)D showed a borderline association with aspartate aminotransferase levels (change -1.17; 95% CI, -1.36 to 0.01). Genetic predisposition to NAFLD was not associated with S-25(OH)D (change 0.13; 95% CI, -1.26 to 0.53). CONCLUSIONS Our findings have clinical implications as they suggest that increased vitamin D levels may play a role in NAFLD prevention in European populations.
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Nuts and seeds consumption and risk of cardiovascular disease, type 2 diabetes and their risk factors: a systematic review and meta-analysis.
Arnesen, EK, Thorisdottir, B, Bärebring, L, Söderlund, F, Nwaru, BI, Spielau, U, Dierkes, J, Ramel, A, Lamberg-Allardt, C, Åkesson, A
Food & nutrition research. 2023;67
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Nuts and seeds consumption is associated with a reduced risk of coronary heart disease (CHD) and cardiovascular disease (CVD). Nuts and seeds contain beneficial components to reduce the risk of CVD and CHD; hence dietary addition may benefit heart health. This systematic review and meta-analysis included sixty studies to analyse the effects of the consumption of nuts and seeds on the incidence of mortality from type 2 diabetes (T2D) and CVD and intermediate cardiometabolic risk factors. High nuts and seed consumption showed a 19% reduction in CVD risk and a 23% reduction in CVD mortality. In addition, high consumption lowered the risk of CHD by 25%. Increased nut consumption up to 30 g/day showed a dose-dependent relationship with reduced risk of CVD. Healthcare professionals can use the results of this study to understand the association between nuts and seeds consumption and CHD, CVD and blood lipid levels. However, further robust studies are required to evaluate the effect of specific nuts and seeds on CHD and CVD risk reduction.
Abstract
OBJECTIVES We aimed to systematically review studies and evaluate the strength of the evidence on nuts/seeds consumption and cardiometabolic diseases and their risk factors among adults. METHODS A protocol was pre-registered in PROSPERO (CRD42021270554). We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to September 20, 2021 for prospective cohort studies and ≥12-week randomized controlled trials (RCTs). Main outcomes were cardiovascular disease (CVD), coronary heart disease (CHD), stroke and type 2 diabetes (T2D), secondary total-/low density lipoprotein (LDL)-cholesterol, blood pressure and glycaemic markers. Data extraction and risk of bias (RoB) assessments (using RoB 2.0 and RoB-NObS) were performed in duplicate. Effect sizes were pooled using random-effects meta-analyses and expressed as relative risk (RR) or weighted mean differences with 95% confidence intervals (CI); heterogeneity quantified as I 2. One-stage dose-response analyses assessed the linear and non-linear associations with CVD, CHD, stroke and T2D. The strength of evidence was classified per the World Cancer Research Fund criteria. RESULTS After screening 23,244 references, we included 42 papers from cohort studies (28 unique cohorts, 1,890,573 participants) and 18 RCTs (2,266 participants). In the cohorts, mainly populations with low consumption, high versus low total nuts/seeds consumption was inversely associated with total CVD (RR 0.81; 95% CI 0.75, 0.86; I 2 = 67%), CVD mortality (0.77; 0.72, 0.82; I 2 = 59.3%), CHD (0.82; 0.76, 0.89; I 2 = 64%), CHD mortality (0.75; 0.65, 0.87; I 2 = 66.9%) and non-fatal CHD (0.85; 0.75, 0.96; I 2 = 62.2%). According to the non-linear dose-response analyses, consumption of 30 g/day of total nuts/seeds was associated with RRs of similar magnitude. For stroke and T2D the summary RR for high versus low intake was 0.91 (95% CI 0.85, 0.97; I 2 = 24.8%) and 0.95 (0.75, 1.21; I 2 = 82.2%). Intake of nuts (median ~50 g/day) lowered total (-0.15 mmol/L; -0.22, -0.08; I 2 = 31.2%) and LDL-cholesterol (-0.13 mmol/L; -0.21, -0.05; I 2 = 68.6%), but not blood pressure. Findings on fasting glucose, HbA1c and insulin resistance were conflicting. The results were robust to sensitivity and subgroup analyses. We rated the associations between nuts/seeds and both CVD and CHD as probable. There was limited but suggestive evidence for no association with stroke. No conclusion could be made for T2D. CONCLUSION There is a probable relationship between consumption of nuts/seeds and lower risk of CVD, mostly driven by CHD, possibly in part through effects on blood lipids. More research on stroke and T2D may affect the conclusions. The evidence of specific nuts should be further investigated.
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10.
Soluble Fiber Supplementation and Serum Lipid Profile: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.
Ghavami, A, Ziaei, R, Talebi, S, Barghchi, H, Nattagh-Eshtivani, E, Moradi, S, Rahbarinejad, P, Mohammadi, H, Ghasemi-Tehrani, H, Marx, W, et al
Advances in nutrition (Bethesda, Md.). 2023
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Dyslipidaemia is considered an important risk factor for cardiovascular disease incidence, characterised by elevated circulating concentrations of blood lipids such as cholesterol and triglycerides (TG). Dietary fibre, particularly water-soluble fibres, has demonstrated efficacy and tolerability in serum lipid management. The aim of this study was to synthesise data from individual investigations and to determine the overall treatment effect of soluble fibre on serum blood lipids. This study is a comprehensive systematic review and a dose-response meta-analysis of 181 studies with 220 treatment arms, including 14,505 participants (7348 cases and 7157 controls). Results show that soluble fibre supplementation improved serum TG, total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein-B concentrations. However, it did not alter serum high-density lipoprotein cholesterol and apolipoprotein-A levels. Furthermore, the meta-analysis showed a significant effect of soluble fibre supplementation on serum TG, total cholesterol, and high-density lipoprotein cholesterol in 15 g/d and low-density lipoprotein cholesterol in 10 g/d. Authors conclude that increasing fibre intake using soluble fibre supplementation could be an effective intervention in the prevention and management of dyslipidaemia, and consequently may contribute to the risk reduction of cardiovascular diseases.
Abstract
To present a comprehensive synthesis of the effect of soluble fiber supplementation on blood lipid parameters in adults, a systematic search was undertaken in PubMed, Scopus, and ISI Web of Science of relevant articles published before November 2021. Randomized controlled trials (RCTs) evaluating the effects of soluble fibers on blood lipids in adults were included. We estimated the change in blood lipids for each 5 g/d increment in soluble fiber supplementation in each trial and then calculated the mean difference (MD) and 95% CI using a random-effects model. We estimated dose-dependent effects using a dose-response meta-analysis of differences in means. The risk of bias and certainty of the evidence was evaluated using the Cochrane risk of bias tool and the Grading Recommendations Assessment, Development, and Evaluation methodology, respectively. A total of 181 RCTs with 220 treatment arms (14,505 participants: 7348 cases and 7157 controls) were included. There was a significant reduction in LDL cholesterol (MD: -8.28 mg/dL, 95% CI: -11.38, -5.18), total cholesterol (TC) (MD: -10.82 mg/dL, 95% CI: -12.98, -8.67), TGs (MD: -5.55 mg/dL, 95% CI: -10.31, -0.79), and apolipoprotein B (Apo-B) (MD: -44.99 mg/L, 95% CI: -62.87, -27.12) after soluble fiber supplementation in the overall analysis. Each 5 g/d increase in soluble fiber supplementation had a significant reduction in TC (MD: -6.11 mg/dL, 95% CI: -7.61, -4.61) and LDL cholesterol (MD: -5.57 mg/dl, 95% CI: -7.44, -3.69). In a large meta-analysis of RCTs, results suggest that soluble fiber supplementation could contribute to the management of dyslipidemia and the reduction of cardiovascular disease risk.