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High-intensity interval training improves metabolic syndrome and body composition in outpatient cardiac rehabilitation patients with myocardial infarction.
Dun, Y, Thomas, RJ, Smith, JR, Medina-Inojosa, JR, Squires, RW, Bonikowske, AR, Huang, H, Liu, S, Olson, TP
Cardiovascular diabetology. 2019;18(1):104
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Metabolic syndrome (MetS) is associated with an eightfold increase in the risk of myocardial infarction (MI), and MI patients who have MetS have an increased risk of other cardiovascular events and recurrent MI. Exercise can improve MetS and is also recommended for patients after MI for rehabilitation. The aim of this retrospective study was to examine the effect of supervised high intensity interval training (HIIT) on MetS and body composition in overweight patients with MI. Of 56 patients who took part in a multidisciplinary rehabilitation program, 42 had engaged in HIIT and 14 in moderate-intensity continuous training (MICT), both groups had 36 supervised sessions over 12 weeks. Compared to MICT, the HIIT group demonstrated greater reductions in MetS. Better improvements in the HIIT group were seen in waist circumference, fasting blood glucose, triglycerides, diastolic blood pressure, body fat and lean mass, compared to the MICT group. There were no significant differences between groups in changes in BMI, HDL cholesterol and systolic blood pressure. The authors concluded that their findings support the use of HIIT to improve MetS in MI patients
Abstract
BACKGROUND To examine the effect of high-intensity interval training (HIIT) on metabolic syndrome (MetS) and body composition in cardiac rehabilitation (CR) patients with myocardial infarction (MI). METHODS We retrospectively screened 174 consecutive patients with MetS enrolled in CR following MI between 2015 and 2018. We included 56 patients who completed 36 CR sessions and pre-post dual-energy X-ray absorptiometry. Of these patients, 42 engaged in HIIT and 14 in moderate-intensity continuous training (MICT). HIIT included 4-8 intervals of high-intensity (30-60 s at RPE 15-17 [Borg 6-20]) and low-intensity (1-5 min at RPE < 14), and MICT included 20-45 min of exercise at RPE 12-14. MetS and body composition variables were compared between MICT and HIIT groups. RESULTS Compared to MICT, HIIT demonstrated greater reductions in MetS (relative risk = 0.5, 95% CI 0.33-0.75, P < .001), MetS z-score (- 3.6 ± 2.9 vs. - 0.8 ± 3.8, P < .001) and improved MetS components: waist circumference (- 3 ± 5 vs. 1 ± 5 cm, P = .01), fasting blood glucose (- 25.8 ± 34.8 vs. - 3.9 ± 25.8 mg/dl, P < .001), triglycerides (- 67.8 ± 86.7 vs. - 10.4 ± 105.3 mg/dl, P < .001), and diastolic blood pressure (- 7 ± 11 vs. 0 ± 13 mmHg, P = .001). HIIT group demonstrated greater reductions in body fat mass (- 2.1 ± 2.1 vs. 0 ± 2.2 kg, P = .002), with increased body lean mass (0.9 ± 1.9 vs. - 0.9 ± 3.2 kg, P = .01) than the MICT. After matching for exercise energy expenditure, HIIT-induced improvements persisted for MetS z-score (P < .001), MetS components (P < .05), body fat mass (P = .002), body fat (P = .01), and lean mass (P = .03). CONCLUSIONS Our data suggest that, compared to MICT, supervised HIIT results in greater improvements in MetS and body composition in MI patients with MetS undergoing CR.
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Dietary fiber intake and glycemic control: coronary artery calcification in type 1 diabetes (CACTI) study.
Basu, A, Alman, AC, Snell-Bergeon, JK
Nutrition journal. 2019;18(1):23
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The incidence of type 1 diabetes and cardiovascular disease, the major vascular complication of diabetes, have been increasing wordwide. The aim of the study is to identify the associations of dietary fibre with glycaemic control. The study is a cross-sectional longitudinal study which enrolled 1257 individuals in the cross-sectional analysis and a total of 990 participants were included in the longitudinal analysis. The participants had no known history of coronary heart disease. Results indicate an inverse association between total fibre intake and the average blood glucose levels for the last two to three months in both diabetic and nondiabetic participants. Authors conclude that their study provides some evidence on the role dietary fibre intake plays on glycaemic control, which is important in the management of type 1 diabetes in patients at high risk of cardiovascular disease.
Abstract
BACKGROUND Dietary fiber has been recommended for glucose control, and typically low intakes are observed in the general population. The role of fiber in glycemic control in reported literature is inconsistent and few reports are available in populations with type 1 diabetes (T1D). METHODS Using data from the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study [n = 1257; T1D: n = 568; non-diabetic controls: n = 689] collected between March 2000 and April 2002, we examined cross-sectional (baseline) and longitudinal (six-year follow-up in 2006-2008) associations of dietary fiber and HbA1c. Participants completed a validated food frequency questionnaire, and a physical examination and fasting biochemical analyses (12 h fast) at baseline visit and at the year 6 visit. We used a linear regression model stratified by diabetes status, and adjusted for age, sex and total calories, and diabetes duration in the T1D group. We also examined correlations of dietary fiber with HbA1c. RESULTS Baseline dietary fiber intake and serum HbA1c in the T1D group were 16 g [median (IQ): 11-22 g) and 7.9 ± 1.3% mean (SD), respectively, and in the non-diabetic controls were 15 g [median (IQ): 11-21 g) and 5.4 ± 0.4%, respectively. Pearson partial correlation coefficients revealed a significant but weak inverse association of total dietary fiber with HbA1c when adjusted for age, sex, diabetes status and total calories (r = - 0.07, p = 0.01). In the adjusted linear regression model at baseline, total dietary fiber revealed a significant inverse association with HbA1c in the T1D group [β ± SE = - 0.32 ± 0.15, p = 0.034], as well as in the non-diabetic controls [- 0.10 ± 0.04, p = 0.009]. However, these results were attenuated after adjustment for dietary carbohydrates, fats and proteins, or for cholesterol and triglycerides. No such significance was observed at the year 6 follow-up, and with the HbA1c changes over 6 years. CONCLUSION Thus, at observed levels of intake, total dietary fiber reveals modest inverse associations with poor glycemic control. Future studies must further investigate the role of overall dietary quality adjusting for fiber-rich foods in T1D management.
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Changes in Gut Microbiota-Related Metabolites and Long-term Successful Weight Loss in Response to Weight-Loss Diets: The POUNDS Lost Trial.
Heianza, Y, Sun, D, Smith, SR, Bray, GA, Sacks, FM, Qi, L
Diabetes care. 2018;41(3):413-419
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Evidence has demonstrated that weight loss contributes to lowering the risk of developing type 2 diabetes among obese patients. The aim of this study was to examine whether diet-induced metabolites were associated with improvements in adiposity and metabolism during a weight-loss diet intervention in 510 overweight and obese individuals. Participants were randomly assigned to one of four diets with varying macronutrient composition to adhere to for six months. Blood samples and anthropometric data were taken at baseline and 6 months to monitor changes. This study found that overweight and obese individuals with reduced choline or L-carnitine levels achieved greater improvements of adiposity and energy metabolism. Based on these results, the authors conclude that metabolites are predictive of patient responsiveness to dietary interventions, and suggest further studies evaluate these effects in the pre-diabetic obese population.
Abstract
OBJECTIVE Adiposity and the gut microbiota are both related to the risk of type 2 diabetes. We aimed to comprehensively examine how changes induced by a weight-loss diet intervention in gut microbiota-related metabolites, such as trimethylamine N-oxide (TMAO) and its precursors (choline and l-carnitine), were associated with improvements in adiposity and regional fat deposition. RESEARCH DESIGN AND METHODS This study included 510 overweight and obese individuals who were randomly assigned one of four diets varying in macronutrient intake. We examined associations of 6-month changes in blood metabolites (TMAO, choline, and l-carnitine) with improvements in body weight (BW), waist circumference (WC), body fat composition, fat distribution, and resting energy expenditure (REE). RESULTS Individuals with a greater reduction of choline (P < 0.0001) and l-carnitine (P < 0.01) rather than TMAO showed significant losses of BW and WC at 6 months. The reduction of choline was significantly predictive of decreases in body fat composition, fat distribution, and REE. Results of sensitivity analysis showed that the baseline diabetes risk status, such as the presence of hyperglycemia (31% of the total participants) and fasting glucose levels, did not modify the associations. Early changes in choline and l-carnitine were significantly predictive of weight loss over 2 years (P < 0.05 for all). Individuals with increases in choline or l-carnitine were 2.35-times (95% CI 1.38, 4.00) or 1.77-times (1.06, 2.95) more likely to fail to lose weight (-5% or more loss) at 2 years. CONCLUSIONS Overweight and obese individuals who showed decreases in circulating choline or l-carnitine levels achieved greater improvements of adiposity and energy metabolism by eating a low-calorie weight-loss diet, suggesting that such metabolites are predictive of individuals' response to the treatment. Further investigations are necessary to confirm our findings, particularly in a population with prediabetes that is more representative of the U.S. population with obesity.
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Circulating bile acids in healthy adults respond differently to a dietary pattern characterized by whole grains, legumes and fruits and vegetables compared to a diet high in refined grains and added sugars: A randomized, controlled, crossover feeding study.
Ginos, BNR, Navarro, SL, Schwarz, Y, Gu, H, Wang, D, Randolph, TW, Shojaie, A, Hullar, MAJ, Lampe, PD, Kratz, M, et al
Metabolism: clinical and experimental. 2018;83:197-204
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Bile acids are produced in the liver and are important for the absorption of fat and fat-soluble vitamins. About 95% of bile acids are reabsorbed. Circulating plasma bile acids can affect glucose metabolism and inflammation, and are thought to play a role in the development of metabolic syndrome. The aim of this study was to evaluate how plasma bile acid levels are influenced by a diet rich in whole grains, legumes, fruit and vegetables (low glycaemic load, GL) compared to a diet high in refined grains and sugar (high GL). The study evaluated data from a previous double-blind randomised, cross over feeding trial. 80 healthy adults had the low or high GL diet for four weeks, and after a four-week washout period, received the other diet for four weeks. Three specific plasma bile acids, which are thought to have a positive impact on glucose metabolism, were higher in the low GL group compared to the high GL group. Some individual plasma bile acids were positively associated with HOMA-IR (a measure of glucose metabolism/insulin resistance). There was no significant association between bile acid concentrations and C-reactive protein (a marker of inflammation). The authors conclude that the increase in certain bile acids on the low GL diet may be beneficial and that this effect may be to some extent mediated by the impact of the higher fibre content of the low GL diet on the gut microbial metabolism, which affects plasma bile acid levels.
Abstract
OBJECTIVE The effects of diets high in refined grains on biliary and colonic bile acids have been investigated extensively. However, the effects of diets high in whole versus refined grains on circulating bile acids, which can influence glucose homeostasis and inflammation through activation of farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5), have not been studied. MATERIALS AND METHODS We conducted a secondary analysis from a randomized controlled crossover feeding trial (NCT00622661) in 80 healthy adults (40 women/40 men, age 18-45 years) from the greater Seattle Area, half of which were normal weight (BMI 18.5-25.0 kg/m2) and half overweight to obese (BMI 28.0-39.9 kg/m2). Participants consumed two four-week controlled diets in randomized order: 1) a whole grain diet (WG diet), designed to be low in glycemic load (GL), high in whole grains, legumes, and fruits and vegetables, and 2) a refined grain diet (RG diet), designed to be high GL, high in refined grains and added sugars, separated by a four-week washout period. Quantitative targeted analysis of 55 bile acid species in fasting plasma was performed using liquid chromatography tandem mass spectrometry. Concentrations of glucose, insulin, and CRP were measured in fasting serum. Linear mixed models were used to test the effects of diet on bile acid concentrations, and determine the association between plasma bile acid concentrations and HOMA-IR and CRP. Benjamini-Hochberg false discovery rate (FDR) < 0.05 was used to control for multiple testing. RESULTS A total of 29 plasma bile acids were reliably detected and retained for analysis. Taurolithocholic acid (TLCA), taurocholic acid (TCA) and glycocholic acid (GCA) were statistically significantly higher after the WG compared to the RG diet (FDR < 0.05). There were no significant differences by BMI or sex. When evaluating the association of bile acids and HOMA-IR, GCA, taurochenodeoxycholic acid, ursodeoxycholic acid (UDCA), 5β‑cholanic acid‑3β,12α‑diol, 5‑cholanic acid‑3β‑ol, and glycodeoxycholic acid (GDCA) were statistically significantly positively associated with HOMA-IR individually, and as a group, total, 12α‑hydroxylated, primary and secondary bile acids were also significant (FDR < 0.05). When stratifying by BMI, chenodeoxycholic acid (CDCA), cholic acid (CA), UDCA, 5β-cholanic acid-3β, deoxycholic acid, and total, 12α-hydroxylated, primary and secondary bile acid groups were significantly positively associated with HOMA-IR among overweight to obese individuals (FDR < 0.05). When stratifying by sex, GCA, CDCA, TCA, CA, UDCA, GDCA, glycolithocholic acid (GLCA), total, primary, 12α‑hydroxylated, and glycine-conjugated bile acids were significantly associated with HOMA-IR among women, and CDCA, GDCA, and GLCA were significantly associated among men (FDR < 0.05). There were no significant associations between bile acids and CRP. CONCLUSIONS Diets with comparable macronutrient and energy composition, but differing in carbohydrate source, affected fasting plasma bile acids differently. Specifically, a diet characterized by whole grains, legumes, and fruits and vegetables compared to a diet high in refined grains and added sugars led to modest increases in concentrations of TLCA, TCA and GCA, ligands for FXR and TGR5, which may have beneficial effects on glucose homeostasis.
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A whole-grain diet reduces peripheral insulin resistance and improves glucose kinetics in obese adults: A randomized-controlled trial.
Malin, SK, Kullman, EL, Scelsi, AR, Haus, JM, Filion, J, Pagadala, MR, Godin, JP, Kochhar, S, Ross, AB, Kirwan, JP
Metabolism: clinical and experimental. 2018;82:111-117
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Literature shows that dietary whole-grain intake is associated with a lower incidence of type 2 diabetes. The aim of the study was to investigate the association between a whole-grain diet and insulin resistance and glucose use in individuals at risk for type 2 diabetes. The study was a randomized, double-blind, controlled crossover trial involving fourteen middle-aged, obese adults at risk for diabetes. Randomisation was carried out prior to metabolic testing. Results indicate that whole-grain intake as part of a mixed-meal diet significantly improved post-prandial (after a meal) glucose metabolism in middle-aged obese adults. Furthermore, both whole-grain and refined-grain interventions induced about 3–6% weight and fat loss. Authors conclude that whole-grain intake effectively promotes glycaemic control by improving insulin action.
Abstract
BACKGROUND Whole-grain intake is associated with lower risk of type 2 diabetes but the mechanisms are unclear. PURPOSE We tested the hypothesis that a WG diet reduces insulin resistance and improves glucose use in individuals at risk for type 2 diabetes compared with an isocaloric-matched refined-grain diet. METHODS A double-blind, randomized, controlled, crossover trial of 14 moderately obese adults (Age, 38 ± 2 y; BMI, 34.0 ± 1.1 kg/m2). Insulin resistance and glucose metabolism was assessed using an oral glucose tolerance test combined with isotopic tracers of [6,6-2H2]-glucose and [U-13C]-glucose, and indirect calorimetry. Peripheral and hepatic insulin resistance was assessed as 1/(rate of disposal/insulin), and endogenous glucose rates of appearance (Ra) iAUC60-240 × insulin iAUC60-240, respectively. Both diets met ADA nutritional guidelines and contained either whole-grain (50 g per 1000 kcal) or equivalent refined-grain. All food was provided for 8 wk. with an 8-10 wk. washout period between diets. RESULTS Post-prandial glucose tolerance, peripheral insulin sensitivity, and metabolic flexibility (insulin-stimulated - fasting carbohydrate oxidation) improvements were greater after whole-grain compared to the refined-grain diet (P < 0.05). Compared to baseline, body fat (~2 kg) and hepatic Ra insulin resistance was reduced by both diets, while fasting glucose and exogenous glucose-meal were unchanged after both interventions. Changes in peripheral insulin resistance and metabolic flexibility correlated with improved glucose tolerance (P < 0.05). CONCLUSION Whole-grains reduced diabetes risk and the mechanisms appear to work through reduced post-prandial blood glucose and peripheral insulin resistance that were statistically linked to enhanced metabolic flexibility.
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Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.
Nagy-Szakal, D, Williams, BL, Mishra, N, Che, X, Lee, B, Bateman, L, Klimas, NG, Komaroff, AL, Levine, S, Montoya, JG, et al
Microbiome. 2017;5(1):44
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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, swollen lymph glands and irritable bowel syndrome (IBS). It is associated with gut bacterial dysbiosis, systemic inflammation and both gastro intestinal (GI) and neurological disturbances. The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. This experiment looked at fecal bacterial samples and metabolic pathway markers in 50 ME/CFS patients and 50 healthy controls. In ME/CFS subgroups, measures of symptom severity including pain, fatigue, and reduced motivation were correlated with the amounts and types of gut bacteria and certain metabolic pathways. Future prospective studies should consider more detailed exploration of IBS subtypes, associated GI symptoms, and their relationship to ME/CFS dysbiosis. This may enable more accurate diagnosis and the development of specific therapeutic strategies.
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. RESULTS Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. CONCLUSIONS Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.
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In a randomized trial in prostate cancer patients, dietary protein restriction modifies markers of leptin and insulin signaling in plasma extracellular vesicles.
Eitan, E, Tosti, V, Suire, CN, Cava, E, Berkowitz, S, Bertozzi, B, Raefsky, SM, Veronese, N, Spangler, R, Spelta, F, et al
Aging cell. 2017;16(6):1430-1433
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Obesity and insulin resistance are associated with accelerated aging and increased risk of many age-related diseases. The risk of many cancers, including prostate cancer, increases with age and being overweight further increases the risk. The aim of the study is to investigate the inhibition of tumour growth through the effect of protein restriction diets and hence, levels of circulating amino acids. The participants of the study were men (n=38) with prostate cancer awaiting prostatectomy surgery. Most of the subjects were overweight with a BMI of 30.45 ± 5.8. They were randomly assigned to either a control diet or a protein restricted diet. In comparison to the control diet, results show that protein restriction increased the levels of receptors (a protein molecule that receives chemical signals from outside a cell) responsible of leptin, the hormone that controls hunger. The results also show that protein restriction can improve the body’s sensitivity to the effects of the insulin in neurons (a nerve cell specialised to transmit information throughout the body). Authors conclude that protein restriction can counteract major age-related diseases.
Abstract
Obesity, metabolic syndrome, and hyperleptinemia are associated with aging and age-associated diseases including prostate cancer. One experimental approach to inhibit tumor growth is to reduce dietary protein intake and hence levels of circulating amino acids. Dietary protein restriction (PR) increases insulin sensitivity and suppresses prostate cancer cell tumor growth in animal models, providing a rationale for clinical trials. We sought to demonstrate that biomarkers derived from plasma extracellular vesicles (EVs) reflect systemic leptin and insulin signaling and respond to dietary interventions. We studied plasma samples from men with prostate cancer awaiting prostatectomy who participated in a randomized trial of one month of PR or control diet. We found increased levels of leptin receptor in the PR group in total plasma EVs and in a subpopulation of plasma EVs expressing the neuronal marker L1CAM. Protein restriction also shifted the phosphorylation status of the insulin receptor signal transducer protein IRS1 in L1CAM+ EVs in a manner suggestive of improved insulin sensitivity. Dietary PR modifies indicators of leptin and insulin signaling in circulating EVs. These findings are consistent with improved insulin and leptin sensitivity in response to PR and open a new window for following physiologic responses to dietary interventions in humans.
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Tracking post-infectious fatigue in clinic using routine Lab tests.
Harvey, JM, Broderick, G, Bowie, A, Barnes, ZM, Katz, BZ, O'Gorman, MRG, Vernon, SD, Fletcher, MA, Klimas, NG, Taylor, R
BMC pediatrics. 2016;16:54
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Chronic fatigue syndrome (CFS) is a complex disease with many different symptoms and there are no definitive tests for diagnosis. This cohort study of 301 adolescents, who had suffered a viral infection, aimed to analyse several commonly used biological markers to determine who may experience CFS symptoms. The results showed variations in several biomarkers, however, decreases in hormones related to the stress response were highly predictive of CFS. Sex hormones and the proportion of immune cells were also markedly disrupted. It was concluded that assessing stress hormones, sex hormones and the proportion of immune cells could be used to diagnose CFS following a viral infection. This study could be used by healthcare professionals to understand that several commonly tested biomarkers could be potentially used to diagnose post-viral CFS.
Abstract
BACKGROUND While biomarkers for chronic fatigue syndrome (CFS) are beginning to emerge they typically require a highly specialized clinical laboratory. We hypothesized that subsets of commonly measured laboratory markers used in combination could support the diagnosis of post-infectious CFS (PI-CFS) in adolescents following infectious mononucleosis (IM) and help determine who might develop persistence of symptoms. METHODS Routine clinical laboratory markers were collected prospectively in 301 mono-spot positive adolescents, 4 % of whom developed CFS (n = 13). At 6, 12, and 24 months post-diagnosis with IM, 59 standard tests were performed including metabolic profiling, liver enzyme panel, hormone profiles, complete blood count (CBC), differential white blood count (WBC), salivary cortisol, and urinalysis. Classification models separating PI-CFS from controls were constructed at each time point using stepwise subset selection. RESULTS Lower ACTH levels at 6 months post-IM diagnosis were highly predictive of CFS (AUC p = 0.02). ACTH levels in CFS overlapped with healthy controls at 12 months, but again showed a trend towards a deficiency at 24 months. Conversely, estradiol levels depart significantly from normal at 12 months only to recover at 24 months (AUC p = 0.02). Finally, relative neutrophil count showed a significant departure from normal at 24 months in CFS (AUC p = 0.01). Expression of these markers evolved differently over time between groups. CONCLUSIONS Preliminary results suggest that serial assessment of stress and sex hormones as well as the relative proportion of innate immune cells measured using standard clinical laboratory tests may support the diagnosis of PI-CFS in adolescents with IM.
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Inhalational Alzheimer's disease: an unrecognized - and treatable - epidemic.
Bredesen, DE
Aging. 2016;8(2):304-13
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Alzheimer’s disease (AD) is the third leading cause of death in the USA, with around 5.2 million Americans diagnosed with AD. Effective treatment with medications has yet to be found. A recent multiple therapy programme (originally known as MEND, now called ReCODE) proposed by Professor Bredesen and team, has shown some promising anecdotal results. Identifying sub-types of AD has been proposed as a means to develop targeted protocols for treatment. Recently, 3 sub-types of AD have been described: Type 1 (inflammatory), Type 2 (non-inflammatory or decreasing brain size) and Type 3 (damage to the outer layer of the cerebrum). This report describes 7 patients with Type 3 AD. Type 3 AD is characterised by exposure to specific toxins (usually inhaled) and is often associated with Chronic Inflammatory Response Syndrome (CIRS). The report provides the symptoms, signs and laboratory values representative of Type 3 AD and could be used by Nutrition Practitioners to help with implementation of appropriate nutrition protocols when working with clients with AD.
Abstract
Alzheimer's disease is one of the most significant healthcare problems today, with a dire need for effective treatment. Identifying subtypes of Alzheimer's disease may aid in the development of therapeutics, and recently three different subtypes have been described: type 1 (inflammatory), type 2 (non-inflammatory or atrophic), and type 3 (cortical). Here I report that type 3 Alzheimer's disease is the result of exposure to specific toxins, and is most commonly inhalational (IAD), a phenotypic manifestation of chronic inflammatory response syndrome (CIRS), due to biotoxins such as mycotoxins. The appropriate recognition of IAD as a potentially important pathogenetic condition in patients with cognitive decline offers the opportunity for successful treatment of a large number of patients whose current prognoses, in the absence of accurate diagnosis, are grave.
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Metabolic profiling distinguishes three subtypes of Alzheimer's disease.
Bredesen, DE
Aging. 2015;7(8):595-600
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The causes of Alzheimer’s Disease (AD) remain incompletely defined and there are currently no truly effective drug therapies available. However, there is growing evidence that disordered blood glucose management and hormonal changes and deficiencies, amongst other things, are implicated in symptom onset. Optimising these various metabolic processes, therefore, may be used as a comprehensive way to avoid cognitive decline or achieve cognitive improvements in symptomatic individuals. This report provides the metabolic results of 3 case studies and suggests 3 different types of AD classification, depending on the individual metabolic profile. Further studies are required to elaborate on the metabolic profiles suggested in this report, however Nutrition Practitioners working with cognitive decline, can use this report as a basis for individualised nutrition protocols to optimise metabolic processes in clients with cognitive decline.
Abstract
The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report that metabolic profiling reveals three Alzheimer's disease subtypes. The first is inflammatory, in which markers such as hs-CRP and globulin:albumin ratio are increased. The second type is non-inflammatory, in which these markers are not increased, but other metabolic abnormalities are present. The third type is a very distinctive clinical entity that affects relatively young individuals, extends beyond the typical Alzheimer's disease initial distribution to affect the cortex widely, is characterized by early non-amnestic features such as dyscalculia and aphasia, is often misdiagnosed or labeled atypical Alzheimer's disease, typically affects ApoE4-negative individuals, and is associated with striking zinc deficiency. Given the involvement of zinc in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling, this syndrome of Alzheimer's-plus with low zinc (APLZ) warrants further metabolic, genetic, and epigenetic characterization.