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Circulating levels of maternal vitamin D and risk of ADHD in offspring: results from the Vitamin D Antenatal Asthma Reduction Trial.
Chu, SH, Huang, M, Kelly, RS, Kachroo, P, Litonjua, AA, Weiss, ST, Lasky-Su, J
International journal of epidemiology. 2022;51(3):910-918
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Acting as both a nutrient and a hormone, vitamin D has been found to play a critical role in neurodevelopment across sensitive periods in utero, infancy and early childhood. Among neurodevelopmental and behavioural disorders in early life, attention-deficit/hyperactivity disorder (ADHD) is the most common among children worldwide. Low levels of circulating 25-hydroxy-vitamin D [25(OH)D] have been shown to associate with prevalent ADHD. The aims of this study were to (i) determine the association between maternal vitamin D levels in the first and third trimesters of pregnancy and the risk of offspring ADHD by age 6 years or later; and (ii) to identify potential sensitive periods in utero during which vitamin D levels might be most important for reducing risk of ADHD. This is an ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART). The VDAART was a randomised, double-blinded, multicentre, clinical trial in which 876 participating mothers were recruited between 10–18 weeks of gestation and assigned to receive either 4400 or 400 IU/day of vitamin D throughout pregnancy. Results show protective associations between maternal 25(OH)D sufficiency in the third trimester and child ADHD, but not at baseline. Furthermore, both at baseline and in the third trimester, there were higher odds of ADHD in male offspring as compared with female offspring with 25(OH)D insufficient mothers (analyses limited by small sample sizes) Authors conclude that higher levels of maternal vitamin D during pregnancy may play a protective role against risk of ADHD in offspring, but further studies are needed to confirm this association and any therapeutic potential therein.
Expert Review
Conflicts of interest:
None
Take Home Message:
Ensure that women in pregnancy, and possibly also those seeking to conceive, have adequate vitamin D status in order to reduce the risk of ADHD in offspring.
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
This paper describes a secondary data analysis from an RCT that looked at the effect of prenatal vitamin D supplementation on risk of childhood asthma in offspring. Enrolled women aged 18–39 years with a history of asthma, eczema or allergic rhinitis, or whose partner (biological father of child) had a history of the aforementioned condition, received either 400 IU or 4400 IU vitamin D daily for the duration of their pregnancy. Offspring follow-up is still ongoing.
Aims
The current study aims were twofold: (i) to determine the association between maternal vitamin D levels in trimesters 1 and 3 and the risk of attention deficit/hyperactivity disorder (ADHD) in offspring diagnosed by age 6 years or later; and (ii) to identify potentially sensitive periods during gestation in which vitamin D levels may be especially important for reducing risk of ADHD.
Methods
The analytical sample included 679 mother-child pairs, from the original sample of 876 participating mothers. No sample size calculation was reported, though the sample was considered representative of the overall RCT study population.
Maternal vitamin D (serum 25(OH)D) was classified as follows
- Highly deficient <12 ng/mL
- Deficient 12 ng/mL to 19.9 ng/mL
- Insufficient 20 ng/mL to 29.9 ng/mL
- Sufficient ≥30 ng/mL
ADHD status was assessed through parental reporting between ages 6 and 9 years.
Results
No baseline associations between a vitamin D sufficient status and offspring ADHD in maternal samples collected during trimester 1 were observed (OR 1.06, 95% CI 0.51–2.19; P.0.871), though this association became statistically significant at trimester 3 (OR 0.47, 95% CI 0.26–0.84; P.0.011). This translated to a 53% less chance of having a child with ADHD at age 6 or later among mothers with vitamin D sufficiency compared with children of mothers with vitamin D deficiency. There was also a linear trend in the protective association of vitamin D sufficiency (≥30 ng/mL) on reduced risk of offspring ADHD at age 6 years or later in data from trimester 3. Stratified analyses revealed a protective association for sufficient maternal vitamin D status and offspring ADHD among males (OR 0.47, 95% CI 0.23–0.94).
Conclusions
The authors concluded that vitamin D sufficiency (≥30 ng/mL) in the 3rd trimester of gestation may decrease the risk of ADHD development in offspring.
Notes: The authors reported no relevant conflicts of interest.
Clinical practice applications:
Ensuring a sufficient vitamin D status by the 3rd trimester of pregnancy may help to lessen the risk of ADHD in offspring. Nutritional therapists and other clinicians working with pregnant women or women looking to conceive should consider checking vitamin D status and providing corrective supplementation and lifestyle advice to augment vitamin D levels where indicated.
Considerations for future research:
The authors of this study postulated that the statistically significant protective association between vitamin D at trimester 3 and ADHD in offspring was not significant in trimester 1 due to a low observed variability in vitamin D status (>75% of women were vitamin D insufficient), and thus the statistical test being underpowered to see difference between groups with sufficient or insufficient status.
Further research could expand upon this hypothesis to test whether vitamin D status in trimester 1, or preconceptually, may offer a protective association for ADHD and other related neurological conditions that may manifest in early life.
Abstract
BACKGROUND Low levels of circulating 25-hydroxy-vitamin D [25(OH)D] have been shown to associate with prevalent attention-deficit/hyperactivity disorder (ADHD), but few studies have examined the association between 25(OH)D during fetal development and risk of childhood ADHD. METHODS Maternal plasma 25(OH)D was measured at 10-18 and 32-38 weeks of gestation, with sufficiency defined as 25(OH)D ≥ 30 ng/ml. Offspring ADHD status between ages 6-9 years was measured by parent report of clinical ADHD diagnosis among 680 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial. Association between maternal 25(OH)D and child ADHD was assessed using logistic regression, adjusting for maternal age, race and ethnicity. Effect modification by offspring sex was also assessed. RESULTS No associations between maternal 25(OH)D at 10-18 weeks of gestation and offspring ADHD were observed. In the third trimester, we observed associations between maternal vitamin D sufficiency and offspring ADHD [odds ratio (OR) 0.47, 95% confidence interval (CI) 0.26-0.84], in addition to maternal 25(OH)D sufficiency category, comparing the deficient (OR 0.34, 95% CI 0.12-0.94), insufficient (OR 0.41, 95% CI 0.15-1.10) and sufficient (OR 0.20, 95% CI 0.08-0.54) categories against highly deficient 25(OH)D, respectively. Stratified analyses revealed a protective association for sufficient maternal 25(OH)D and child ADHD among males (OR 0.47, 95% CI 0.23-0.94); the synergy index for additive effect modification of risk was 1.78 (95% CI 0.62-5.08). CONCLUSIONS Higher levels of maternal vitamin D in the third trimester are associated with lower risk of ADHD in offspring, with modest evidence for a stronger effect among male offspring. However, larger studies will be necessary to confirm these findings.
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Health behavior patterns of sugar-sweetened beverage consumption among Brazilian adolescents in a nationally representative school-based study.
Rocha, LL, Pessoa, MC, Gratão, LHA, Carmo, ASD, Cunha, CF, Oliveira, TRPR, Mendes, LL
PloS one. 2021;16(1):e0245203
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Sugar sweetened beverages (SSB) are ultra-processed foods containing several man-made chemicals, which heavily feature in the diets of adolescents in many developing countries. This cross-sectional study of 74,589 adolescents aimed to determine health behaviour patterns that affect SSB consumption to focus education and policy efforts to reduce consumption. The results showed that most adolescents who consumed SSB’s had higher consumption of processed foods, more screen time, more days of alcoholic beverage consumption, were more likely to purchase food from the school canteen, and a smoking habit. Those who had a higher consumption of water, minimally processed foods and frequent physical activity were less likely to consume SSB’s. It was concluded that healthy habits can aid implementation of other beneficial health behaviours. This study could be used by healthcare professionals to understand the importance of adopting healthy habits to decrease SSB and ultra-processed food consumption.
Abstract
Studies on sugar-sweetened beverage consumption patterns can help in the individual and population level management of chronic non-communicable diseases and other conditions. This study aimed to identify the association between health behavior patterns and the consumption of sugar-sweetened beverages among Brazilian adolescents from a nationally representative school-based study. A cross-sectional study analyzed data from 71,553 adolescents aged 12-17 years who attended public and private schools in Brazilian cities, from the Study of Cardiovascular Risk in Adolescents. Principal component analysis was performed to identify health behavior patterns, and ordered logistic regression was performed to identify the association between health behavior patterns and sugar-sweetened beverage consumption. Sugar-sweetened beverage consumption (mL/day) was used as the dependent variable. The analyses were performed using Stata software version 14.0 with a significance level of 0.05. Patterns 2 (alcoholic beverage and smoking habit) and 3 (ultra-processed food and screen time) of health behaviors and regularly purchasing snacks in the school cafeteria increased the odds of sugar-sweetened beverage consumption, while pattern 1 (water, unprocessed and minimally processed food and physical activity) decreased these odds. The adoption of healthy habits can indirectly stimulate the adoption of other habits beneficial to health. These results indicate the importance of adopting a set of regulatory measures to reduce sugar-sweetened beverage consumption.
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Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors.
Merino, J, Jablonski, KA, Mercader, JM, Kahn, SE, Chen, L, Harden, M, Delahanty, LM, Araneta, MRG, Walford, GA, Jacobs, SBR, et al
Diabetes. 2020;69(1):112-120
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Individual risk of Coronary Artery Disease (CAD) and type 2 diabetes reflects the interplay between lifestyle behaviours acting on a backdrop of genetic predisposition. The aim of this study was to examine whether type 2 diabetes prevention strategies, either an intensive lifestyle intervention (ILS) or metformin treatment (MET), modify the association between CAD genetic risk and cardiometabolic risk factors (CRFs) in participants at high risk of type 2 diabetes. The study is a randomised controlled trial were participants were randomly allocated to one of the three groups; ILS (n = 1,079), MET (850 mg twice daily [n = 1,073]), or placebo (n = 1,082). Results indicate that there weren’t major significant differences in baseline characteristics, except for lower high-density lipoprotein and higher triglyceride in the placebo individuals compared with individuals assigned to MET or ILS. In fact, either an ILS or MET has a beneficial effect on 1-year change in different CRFs. Authors conclude that type 2 diabetes–preventive strategies for individuals at high risk of type 2 diabetes provide beneficial effects on CRFs regardless of CAD genetic risk profile.
Abstract
Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (P interaction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.
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Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes.
Zhu, L, She, ZG, Cheng, X, Qin, JJ, Zhang, XJ, Cai, J, Lei, F, Wang, H, Xie, J, Wang, W, et al
Cell metabolism. 2020;31(6):1068-1077.e3
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The novel coronavirus disease 2019 (COVID-19) is caused by infection from the newly emerged, highly contagious coronavirus SARS-CoV-2. The aim of this study was to analyse the association between plasma glucose levels and clinic outcomes in COVID-19 patients with type 2 diabetes (T2D). The study is a retrospective longitudinal, multi-centre study from a cohort of 7,337 COVID-19 cases enrolled among 19 hospitals. Results show that patients with pre-existing T2D received significantly more intensive integrated treatments to manage their symptoms of COVID-19 than the non-diabetic subjects. Furthermore, findings indicate that well-controlled blood glucose was associated with a markedly improved outcome of patients with COVID-19 and pre-existing T2D. Authors conclude that T2D is an important risk factor for COVID-19 progression and adverse endpoints, and well-controlled blood glucose is associated with a significant reduction in the composite adverse outcomes and death.
Abstract
Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.
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Effect of a Nutritional and Behavioral Intervention on Energy-Reduced Mediterranean Diet Adherence Among Patients With Metabolic Syndrome: Interim Analysis of the PREDIMED-Plus Randomized Clinical Trial.
Sayón-Orea, C, Razquin, C, Bulló, M, Corella, D, Fitó, M, Romaguera, D, Vioque, J, Alonso-Gómez, ÁM, Wärnberg, J, Martínez, JA, et al
JAMA. 2019;322(15):1486-1499
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Excess caloric intake and poor nutritional quality are associated with overweight and obesity. A traditional Mediterranean diet has been shown to reduce all-cause mortality, and in particular to reduce risk of cardiovascular disease, type 2 diabetes mellitus and overweight. The aim of this randomised, prospective, single-blinded study was to evaluate the effectiveness of an intensive lifestyle intervention programme in 6874 overweight or obese men and women with metabolic syndrome in Spain. The intervention group was advised on an energy-reduced Mediterranean diet and exercise and received behavioural support, with initial group sessions and interviews, and monthly follow-up phone calls for one year. The control group received advice on a Mediterranean diet and usual care, with 6 monthly follow-ups. After 12 months, the more intensively counselled patients showed a significantly better adherence to an energy-reduced Mediterranean diet than the control group. They had greater reductions in refined grains, pastries, red and processed meats and greater increases in vegetable, fruit and nut consumption than the control group. The intervention group had also better improvements in cardiovascular risk factors.
Abstract
Importance: High-quality dietary patterns may help prevent chronic disease, but limited data exist from randomized trials about the effects of nutritional and behavioral interventions on dietary changes. Objective: To assess the effect of a nutritional and physical activity education program on dietary quality. Design, Setting, and Participants: Preliminary exploratory interim analysis of an ongoing randomized trial. In 23 research centers in Spain, 6874 men and women aged 55 to 75 years with metabolic syndrome and no cardiovascular disease were enrolled in the trial between September 2013 and December 2016, with final data collection in March 2019. Interventions: Participants were randomized to an intervention group that encouraged an energy-reduced Mediterranean diet, promoted physical activity, and provided behavioral support (n = 3406) or to a control group that encouraged an energy-unrestricted Mediterranean diet (n = 3468). All participants received allotments of extra-virgin olive oil (1 L/mo) and nuts (125 g/mo) for free. Main Outcomes and Measures: The primary outcome was 12-month change in adherence based on the energy-reduced Mediterranean diet (er-MedDiet) score (range, 0-17; higher scores indicate greater adherence; minimal clinically important difference, 1 point). Results: Among 6874 randomized participants (mean [SD] age, 65.0 [4.9] years; 3406 [52%] men), 6583 (96%) completed the 12-month follow-up and were included in the main analysis. The mean (SD) er-MedDiet score was 8.5 (2.6) at baseline and 13.2 (2.7) at 12 months in the intervention group (increase, 4.7 [95% CI, 4.6-4.8]) and 8.6 (2.7) at baseline and 11.1 (2.8) at 12 months in the control group (increase, 2.5 [95% CI, 2.3-2.6]) (between-group difference, 2.2 [95% CI, 2.1-2.4]; P < .001). Conclusions and Relevance: In this preliminary analysis of an ongoing trial, an intervention that encouraged an energy-reduced Mediterranean diet and physical activity, compared with advice to follow an energy-unrestricted Mediterranean diet, resulted in a significantly greater increase in diet adherence after 12 months. Further evaluation of long-term cardiovascular effects is needed. Trial Registration: isrctn.com Identifier: ISRCTN89898870.
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Association between consumption of ultra-processed foods and serum C-reactive protein levels: cross-sectional results from the ELSA-Brasil study.
Lopes, AEDSC, Araújo, LF, Levy, RB, Barreto, SM, Giatti, L
Sao Paulo medical journal = Revista paulista de medicina. 2019;137(2):169-176
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Low grade chronic inflammation has been linked to many diseases. It can be measured using bio-markers such as C-reactive protein. Studies have shown that there may be a direct association between consumption of ultra-processed foods and the levels of the inflammatory marker C-reactive protein (CRP). The aim of this study was to investigate whether the consumption of ultra-processed foods is associated with CRP levels, regardless of total energy intake, among men and women. In addition, its aim was to determine whether this association is independent from body mass index (BMI). It was a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health. This is a multi-centre cohort and 15105 adults (aged 35-74) participated. The findings suggest that the positive association of ultra-processed food consumption with CRP levels among women seems to be mediated by the presence of adiposity. The study concludes that cutting back on ultra-processed foods can decrease chronic low-grade inflammation, even if through reducing obesity. This reinforces the importance of public policies aimed towards restricting the availability of ultra-processed foods.
Abstract
BACKGROUND There may be a direct association between consumption of ultra-processed foods and C-reactive protein (CRP) levels, under the assumption that the high glycemic index of these food products could stimulate the entire chronic inflammation cascade, along with an indirect association mediated by obesity. The types of food consumed, including ultra-processed products, strongly influence obesity, and are also associated with higher serum CRP levels. OBJECTIVE Our aim was to investigate whether the caloric contribution of ultra-processed foods to diet is associated with CRP levels, independent of body mass index (BMI). DESIGN AND SETTING Cross-sectional analysis on the Longitudinal Study of Adult Health (ELSA-Brasil) baseline cohort (2008-2010). METHODS Dietary information, obtained through a food frequency questionnaire, was used to estimate the percentage of energy contribution from ultra-processed food to individuals' total caloric intake. CRP levels were the response variable. Sex-specific associations were estimated using generalized linear models with gamma distribution and log-link function. RESULTS Ultra-processed food accounted for 20% of total energy intake. Among men, after adjustments for sociodemographic characteristics, there was no association between ultra-processed food intake and CRP levels. Among women, after adjustment for sociodemographic characteristics, smoking and physical activity, the highest tercile of ultra-processed food intake was associated with mean CRP levels that were 14% higher (95% confidence interval: 1.04-1.24) than those of the lowest tercile. However, after considering BMI, this association lost statistical significance. CONCLUSION Our findings suggest that the positive association of ultra-processed food consumption with CRP levels among women seems to be mediated by the presence of adiposity.
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A randomized, double blind, placebo controlled, multicenter clinical trial to assess the efficacy and safety of Emblica officinalis extract in patients with dyslipidemia.
Upadya, H, Prabhu, S, Prasad, A, Subramanian, D, Gupta, S, Goel, A
BMC complementary and alternative medicine. 2019;19(1):27
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Emblica officinalis (Amla or Indian gooseberry) is a fruit that has been traditionally used in Ayurvedic medicine. It has been shown to be effective in the management of dyslipidemia (abnormal fat metabolism), a risk factor for heart disease, in animal models and in pilot clinical studies without major side effects. This multicenter, randomised, placebo controlled, double blind clinical trial was designed to evaluate the efficacy and safety of a proprietary full spectrum amla extract (containing pulp and seeds) in patients with dyslipidemia. 98 patients were enrolled and all completed the 12 week study. None of them were taking any medication for their dyslipidaemia. All the patients enrolled in the study were also asked to initiate lifestyle changes (healthy diet with exercise at least 4 days a week). Apart from conventional lipid parameters, the investigators also measured a number of other parameters relevant to heart disease, including the atherogenic index of plasma (AIP, a marker of heart disease risk). Compared to the placebo group the amla group had significantly greater reductions in triglycerides, LDL-cholesterol, VLDL-cholesterol and the atherogenic index of plasma (AIP, a better predictor of heart disease risk). There were no significant changes in HDL-cholesterol, CoQ10 (lowering of CoQ10 is a concern with many cholesterol lowering drugs), homocysteine, thyroid stimulating hormone (TSH) or fasting blood glucose. Four non-serious adverse events were observed: mild headache, mild fever, two times gastritis (all resolved with standard treatment), three were in the placebo group, one in the amla group. There were no changes in routine blood tests and vital signs (blood pressure, heart rate, temperature, respiratory rate). The authors conclude that the amla extract has significant potential to improve dyslipidaemia without side effects commonly seen with cholesterol lowering drugs.
Abstract
BACKGROUND Dyslipidemia is one of the most frequently implicated risk factors for development of atherosclerosis. This study evaluated the efficacy of amla (Emblica officinalis) extract (composed of polyphenols, triterpenoids, oils etc. as found in the fresh wild amla fruit) in patients with dyslipidemia. METHODS A total of 98 dyslipidemic patients were enrolled and divided into amla and placebo groups. Amla extract (500 mg) or a matching placebo capsule was administered twice daily for 12 weeks to the respective group of patients. The patients were followed up for 12 weeks and efficacy of study medication was assessed by analyzing lipid profile. Other parameters evaluated were apolipoprotein B (Apo B), apolipoprotein A1 (Apo A1), Coenzyme Q10 (CoQ10), high-sensitive C-reactive protein (hsCRP), fasting blood sugar (FBS), homocysteine and thyroid stimulating hormone (TSH). RESULTS In 12 weeks, the major lipids such as total cholesterol (TC) (p = 0.0003), triglyceride (TG) (p = 0.0003), low density lipoprotein cholesterol (LDL-C) (p = 0.0064) and very low density lipoprotein cholesterol (VLDL-C) (p = 0.0001) were significantly lower in amla group as compared to placebo group. Additionally, a 39% reduction in atherogenic index of the plasma (AIP) (p = 0.0177) was also noted in amla group. The ratio of Apo B to Apo A1 was reduced more (p = 0.0866) in the amla group as compared to the placebo. There was no significant change in CoQ10 level of amla (p = 0.2942) or placebo groups (p = 0.6744). Although there was a general trend of FBS reduction, the numbers of participants who may be classified as pre-diabetes and diabetes groups (FBS > 100 mg/dl) in the amla group were only 8. These results show that the amla extract used in the study is potentially a hypoglycaemic as well. However, this needs reconfirmation in a larger study. CONCLUSIONS The Amla extract has shown significant potential in reducing TC and TG levels as well as lipid ratios, AIP and apoB/apo A-I in dyslipidemic persons and thus has scope to treat general as well as diabetic dyslipidemia. A single agent to reduce cholesterol as well as TG is rare. Cholesterol reduction is achieved without concomitant reduction of Co Q10, in contrast to what is observed with statins. TRIAL REGISTRATION Registered with Clinical Trials Registry- India at www.ctri.nic.in (Registration number: CTRI/2015/04/005682 ) on 8 April 2015 (retrospectively registered).
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Effect of a Low Free Sugar Diet vs Usual Diet on Nonalcoholic Fatty Liver Disease in Adolescent Boys: A Randomized Clinical Trial.
Schwimmer, JB, Ugalde-Nicalo, P, Welsh, JA, Angeles, JE, Cordero, M, Harlow, KE, Alazraki, A, Durelle, J, Knight-Scott, J, Newton, KP, et al
JAMA. 2019;321(3):256-265
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The prevalence of non-alcoholic fatty liver disease (NAFLD) among children in the United States is increasing and evidence supports a role for dietary sugar in the development and progression of NAFLD. This open-label, randomised clinical trial using a feeding study design was performed to test the hypothesis that restricting free sugar would improve NAFLD in children. Children in the intervention group, who were provided all food for the 8 week intervention, received less than 3% of daily calories from sugar. The control group continued with their usual diet. Study visits were conducted at baseline and at 4 and 8 weeks after start of the intervention. The mean decrease in hepatic steatosis (a sign of NAFLD) from baseline to week 8 was significantly greater for the intervention diet group compared with the usual diet group. Liver enzymes, total cholesterol, weight/body mass index and systolic blood pressure also improved more in the low sugar group than in the usual diet group. There was no difference in markers for blood sugar control and other lipid parameters. The authors conclude that these findings suggest a potential benefit of a low sugar diet for children with NAFLD, but state that further research is needed to assess long-term and clinical outcomes.
Abstract
Importance: Pediatric guidelines for the management of nonalcoholic fatty liver disease (NAFLD) recommend a healthy diet as treatment. Reduction of sugary foods and beverages is a plausible but unproven treatment. Objective: To determine the effects of a diet low in free sugars (those sugars added to foods and beverages and occurring naturally in fruit juices) in adolescent boys with NAFLD. Design, Setting, and Participants: An open-label, 8-week randomized clinical trial of adolescent boys aged 11 to 16 years with histologically diagnosed NAFLD and evidence of active disease (hepatic steatosis >10% and alanine aminotransferase level ≥45 U/L) randomized 1:1 to an intervention diet group or usual diet group at 2 US academic clinical research centers from August 2015 to July 2017; final date of follow-up was September 2017. Interventions: The intervention diet consisted of individualized menu planning and provision of study meals for the entire household to restrict free sugar intake to less than 3% of daily calories for 8 weeks. Twice-weekly telephone calls assessed diet adherence. Usual diet participants consumed their regular diet. Main Outcomes and Measures: The primary outcome was change in hepatic steatosis estimated by magnetic resonance imaging proton density fat fraction measurement between baseline and 8 weeks. The minimal clinically important difference was assumed to be 4%. There were 12 secondary outcomes, including change in alanine aminotransferase level and diet adherence. Results: Forty adolescent boys were randomly assigned to either the intervention diet group or the usual diet group (20 per group; mean [SD] age, 13.0 [1.9] years; most were Hispanic [95%]) and all completed the trial. The mean decrease in hepatic steatosis from baseline to week 8 was significantly greater for the intervention diet group (25% to 17%) vs the usual diet group (21% to 20%) and the adjusted week 8 mean difference was -6.23% (95% CI, -9.45% to -3.02%; P < .001). Of the 12 prespecified secondary outcomes, 7 were null and 5 were statistically significant including alanine aminotransferase level and diet adherence. The geometric mean decrease in alanine aminotransferase level from baseline to 8 weeks was significantly greater for the intervention diet group (103 U/L to 61 U/L) vs the usual diet group (82 U/L to 75 U/L) and the adjusted ratio of the geometric means at week 8 was 0.65 U/L (95% CI, 0.53 to 0.81 U/L; P < .001). Adherence to the diet was high in the intervention diet group (18 of 20 reported intake of <3% of calories from free sugar during the intervention). There were no adverse events related to participation in the study. Conclusions and Relevance: In this study of adolescent boys with NAFLD, 8 weeks of provision of a diet low in free sugar content compared with usual diet resulted in significant improvement in hepatic steatosis. However, these findings should be considered preliminary and further research is required to assess long-term and clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02513121.
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Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial.
Pouteau, E, Kabir-Ahmadi, M, Noah, L, Mazur, A, Dye, L, Hellhammer, J, Pickering, G, Dubray, C
PloS one. 2018;13(12):e0208454
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Magnesium (Mg) plays a role in over 600 biochemical reactions. It is depleted during stress, and a lack of Mg increases the release of stress hormones, leading to a vicious cycle of lowered resistance to stress and further Mg depletion. Vitamin B6 influences neurotransmitters involved in depression and anxiety, and may improve the uptake of magnesium into cells. The aim of this randomised control trial was to evaluate the effects of combined magnesium and vitamin B6 supplementation in stressed people with low blood levels of magnesium. 260 adults aged 18-50 completed the 8-week study. At the beginning of the trial, all participants had suboptimal blood serum magnesium (0.45 mmol/L to 0.85 mmol/L) and reported moderate to extremely severe stress levels. Participants were divided into two groups. One group received magnesium supplementation (465mg magnesium lactate dihydrate, equivalent to 300mg elemental magnesium; Mg), whilst the other received a combined magnesium and vitamin B6 supplement (470 mg magnesium lactate dihydrate plus 5 mg pyridoxine hydrochloride; Mg-B6). After 8 weeks, the Mg-B6 group reported a reduction in stress levels of 44.9%, and the Mg group reported a reduction of 42.4%, with no statistical difference between the two groups overall. However, participants who reported severe or extremely severe stress levels at the start of the study experienced 24% greater improvement with Mg-B6 versus Mg. Researchers concluded that in people with low magnesium levels experiencing severe or extremely severe stress, combining vitamin B6 with magnesium appears to be of greater benefit than supplementing Mg alone.
Abstract
INTRODUCTION Animal and clinical studies suggest complementary effects of magnesium and high-dose pyridoxine (vitamin B6) on stress reduction. This is the first randomized trial evaluating the effects of combined magnesium and vitamin B6 supplementation on stress in a stressed population with low magnesemia using a validated measure of perceived stress. METHODS In this Phase IV, investigator-blinded trial (EudraCT: 2015-003749-24), healthy adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 and serum magnesium concentration 0.45 mmol/L-0.85 mmol/L, were randomized 1:1 to magnesium-vitamin B6 combination (Magne B6 [Mg-vitamin B6]; daily dose 300 mg and 30 mg, respectively) or magnesium alone (Magnespasmyl [Mg]; daily dose 300 mg). Outcomes included change in DASS-42 stress subscale score from baseline to Week 8 (primary endpoint) and Week 4, and incidence of adverse events (AEs). RESULTS In the modified intention-to-treat analysis (N = 264 subjects), both treatment arms substantially reduced DASS-42 stress subscale score from baseline to Week 8 (Mg-vitamin B6, 44.9%; Mg 42.4%); no statistical difference between arms was observed (p>0.05). An interaction (p = 0.0097) between baseline stress level and treatment warranted subgroup analysis (as per statistical plan); adults with severe/extremely severe stress (DASS-42 stress subscale score ≥25; N = 162) had a 24% greater improvement with Mg-vitamin B6 versus Mg at Week 8 (3.16 points, 95% CI 0.50 to 5.82, p = 0.0203). Consistent results were observed in the per protocol analysis and at Week 4. Overall, 12.1% of Mg-vitamin B6 treated and 17.4% of Mg-treated subjects experienced AEs potentially treatment related. CONCLUSIONS These findings suggest oral Mg supplementation alleviated stress in healthy adults with low magnesemia and the addition of vitamin B6 to Mg was not superior to Mg supplementation alone. With regard to subjects with severe/extremely severe stress, this study provides clinical support for greater benefit of Mg combined with vitamin B6.
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Men and women respond differently to rapid weight loss: Metabolic outcomes of a multi-centre intervention study after a low-energy diet in 2500 overweight, individuals with pre-diabetes (PREVIEW).
Christensen, P, Meinert Larsen, T, Westerterp-Plantenga, M, Macdonald, I, Martinez, JA, Handjiev, S, Poppitt, S, Hansen, S, Ritz, C, Astrup, A, et al
Diabetes, obesity & metabolism. 2018;20(12):2840-2851
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Overweight and obesity are major risk factors for developing type 2 diabetes mellitus. Men and women respond differently to weight loss programmes, with men typically losing more weight and more abdominal fat, whilst women lose more subcutaneous fat. The aim of this large multinational study was to compare the effects of weight loss induced by an 8‐week low energy diet on metabolic outcomes in overweight men and women with prediabetes. Study participants followed the Cambridge Weight Plan which is based on four formula meals, with a total of approximately 810kcal, per day, for eight weeks. Small amounts of non-starchy vegetables were allowed, as were psyllium husks in case of digestive problems. Men lost significantly more weight than women, 11.8% versus 10.3%. Insulin resistance improved similarly in men and women, but metabolic syndrome score improved more in men than in women. Men lost more fat than women and generally had more beneficial metabolic changes. Women had higher reductions in fat-free mass, bone mineral content and HDL cholesterol than men, raising the question whether rapid weight loss may have negative longer term effects for women.
Abstract
AIMS: The PREVIEW lifestyle intervention study (ClinicalTrials.gov Identifier: NCT01777893) is, to date, the largest, multinational study concerning prevention of type-2 diabetes. We hypothesized that the initial, fixed low-energy diet (LED) would induce different metabolic outcomes in men vs women. MATERIALS AND METHODS All participants followed a LED (3.4 MJ/810 kcal/daily) for 8 weeks (Cambridge Weight Plan). Participants were recruited from 8 sites in Europe, Australia and New Zealand. Those eligible for inclusion were overweight (BMI ≥ 25 kg/m2 ) individuals with pre-diabetes according to ADA-criteria. Outcomes of interest included changes in insulin resistance, fat mass (FM), fat-free mass (FFM) and metabolic syndrome Z-score. RESULTS In total, 2224 individuals (1504 women, 720 men) attended the baseline visit and 2020 (90.8%) completed the follow-up visit. Following the LED, weight loss was 16% greater in men than in women (11.8% vs 10.3%, respectively) but improvements in insulin resistance were similar. HOMA-IR decreased by 1.50 ± 0.15 in men and by 1.35 ± 0.15 in women (ns). After adjusting for differences in weight loss, men had larger reductions in metabolic syndrome Z-score, C-peptide, FM and heart rate, while women had larger reductions in HDL cholesterol, FFM, hip circumference and pulse pressure. Following the LED, 35% of participants of both genders had reverted to normo-glycaemia. CONCLUSIONS An 8-week LED induced different effects in women than in men. These findings are clinically important and suggest gender-specific changes after weight loss. It is important to investigate whether the greater decreases in FFM, hip circumference and HDL cholesterol in women after rapid weight loss compromise weight loss maintenance and future cardiovascular health.