BACKGROUND: The global pattern of varying prevalence of diseases of affluence, such as obesity, cardiovascular disease and diabetes, suggests that some environmental factor specific to agrarian societies could initiate these diseases. PRESENTATION OF THE HYPOTHESIS: We propose that a cereal-based diet could be such an environmental factor. Through previous studies in archaeology and molecular evolution we conclude that humans and the human leptin system are not specifically adapted to a cereal-based diet, and that leptin resistance associated with diseases of affluence could be a sign of insufficient adaptation to such a diet. We further propose lectins as a cereal constituent with sufficient properties to cause leptin resistance, either through effects on metabolism central to the proper functions of the leptin system, and/or directly through binding to human leptin or human leptin receptor, thereby affecting the function. TESTING THE HYPOTHESIS: Dietary interventions should compare effects of agrarian and non-agrarian diets on incidence of diseases of affluence, related risk factors and leptin resistance. A non-significant (p= .10) increase of cardiovascular mortality was noted in patients advised to eat more whole-grain cereals. Our lab conducted a study on 24 domestic pigs in which a cereal-free hunter-gatherer diet promoted significantly higher insulin sensitivity, lower diastolic blood pressure and lower C-reactive protein as compared to a cereal-based swine feed. Testing should also evaluate the effects of grass lectins on the leptin system in vivo by diet interventions, and in vitro in various leptin and leptin receptor models. Our group currently conducts such studies. IMPLICATIONS OF THE HYPOTHESIS: If an agrarian diet initiates diseases of affluence it should be possible to identify the responsible constituents and modify or remove them so as to make an agrarian diet healthier.
Other papers by authors:
Tommy Jonsson,
Yvonne Granfeldt,
Bo Ahren,
Ulla-Carin Branell,
Gunvor Palsson,
Anita Hansson,
Margareta Soderstrom,
Staffan Lindeberg
ABSTRACT: BACKGROUND: Our aim was to compare the effects of a Paleolithic ('Old Stone Age') diet and a diabetes diet as generally recommended on risk factors for cardiovascular disease in patients with type 2 diabetes not treated with insulin. METHODS: In a randomized cross-over study, 13 patients with type 2 diabetes, 3 women and 10 men, were instructed to eat a Paleolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; and a Diabetes diet designed in accordance with dietary guidelines during two consecutive 3-month periods. Outcome variables included changes in weight, waist circumference, serum lipids, C-reactive protein, blood pressure, glycated haemoglobin (HbA1c), and areas under the curve for plasma glucose and plasma insulin in the 75g oral glucose tolerance test. Dietary intake was evaluated by use of 4-day weighed food records. RESULTS: Study participants had on average a diabetes duration of 9 years, a mean HbA1c of 6,6 % units by Mono-S standard and were usually treated with metformin alone (3 subjects) or metformin in combination with a sulfonylurea (3 subjects) or a thiazolidinedione (3 subjects). Mean average dose of metformin was 1031 mg per day. Compared to the diabetes diet, the Paleolithic diet resulted in lower mean values of HbA1c (- .4% units, p= .01), triacylglycerol (- .4 mmol/L, p= .003), diastolic blood pressure (-4 mmHg, p= .03), weight (-3 kg, p= .01), BMI (-1 kg/m2, p= .04) and waist circumference (-4 cm, p= .02), and higher mean values of high density lipoprotein cholesterol (+ .08 mmol/L, p= .03). The Paleolithic diet was mainly lower in cereals and dairy products, and higher in fruits, vegetables, meat and eggs, as compared with the Diabetes diet. Further, the Paleolithic diet was lower in total energy, energy density, carbohydrate, dietary glycemic load, saturated fatty acids and calcium, and higher in unsaturated fatty acids, dietary cholesterol and several vitamins. Dietary GI was slightly lower in the Paleolithic diet (GI=50) than in the Diabetic diet (GI=55). CONCLUSIONS: Over a 3-month study period, a Paleolithic diet improved glycemic control and several cardiovascular risk factors compared to a Diabetes diet in patients with type 2 diabetes. Trial registration ClinicalTrials.gov NCT00435240.
Tommy Jonsson,
Bo Ahren,
Giovanni Pacini,
Frank Sundler,
Nils Wierup,
Stig Steen,
Trygve Sjoberg,
Martin Ugander,
Johan Frostegard,
Leif Goransson,
Staffan Lindeberg
ABSTRACT: BACKGROUND: A Paleolithic diet has been suggested to be more in concordance with human evolutionary legacy than a cereal based diet. This might explain the lower incidence among hunter-gatherers of diseases of affluence such as type 2 diabetes, obesity and cardiovascular disease. The aim of this study was to experimentally study the long-term effect of a Paleolithic diet on risk factors for these diseases in domestic pigs. We examined glucose tolerance, post-challenge insulin response, plasma C-reactive protein and blood pressure after 15 months on Paleolithic diet in comparison with a cereal based swine feed. METHODS: Upon weaning twenty-four piglets were randomly allocated either to cereal based swine feed (Cereal group) or cereal free Paleolithic diet consisting of vegetables, fruit, meat and a small amount of tubers (Paleolithic group). At 17 months of age an intravenous glucose tolerance test was performed and pancreas specimens were collected for immunohistochemistry. Group comparisons of continuous variables were made by use of the t-test. P< .05 was chosen for statistical significance. Simple and multivariate correlations were evaluated by use of linear regression analysis. RESULTS: At the end of the study the Paleolithic group weighed 22% less and had 43% lower subcutaneous fat thickness at mid sternum. No significant difference was seen in fasting glucose between groups. Dynamic insulin sensitivity was significantly higher (p= .004) and the insulin response was significantly lower in the Paleolithic group (p= .001). The geometric mean of C-reactive protein was 82% lower (p= .0007) and intra-arterial diastolic blood pressure was 13% lower in the Paleolithic group (p= .007). In evaluations of multivariate correlations, diet emerged as the strongest explanatory variable for the variations in dynamic insulin sensitivity, insulin response, C-reactive protein and diastolic blood pressure when compared to other relevant variables such as weight and subcutaneous fat thickness at mid sternum. There was no obvious immunohistochemical difference in pancreatic islets between the groups, but leukocytes were clearly more frequent in sampled pancreas from the Cereal group. CONCLUSIONS: This study in domestic pigs suggests that a Paleolithic diet conferred higher insulin sensitivity, lower C-reactive protein and lower blood pressure when compared to a cereal based diet.
Nancy Agmon-Levin,
Porat Katz Bat-Sheva,
Ori Barzilai,
Maya Ram,
Staffan Lindeberg,
Johan Frostegård,
Yehuda Shoenfeld
Department of Medicine "B", Sheba Medical Center, Tel-Hashomer, Israel.
The objective of our study was to determine the prevalence of anti-infectious agent antibodies and autoantibodies in a unique non-Westernized population from Kitava, Papua New Guinea (PNG), compared to Western populations. We matched 120 serum samples from Kitavans with 437 samples from four healthy control groups. Sera were tested for the presence of anti-infectious agent antibodies (treponema, toxoplsmosis, Epstein-Barr virus, cytomegalovirus, rubella) and autoantiobodies [anti-double-stranded (ds)DNA, anti-chromatin, anti-ribonucleoprotein (RNP), anti-SSB, anti-SSA, anti-Scl-70, anti-Smith, anti-centromer, anti-SmRNP, anti-Jo-1, and anti-ribosomal-P] using the Bio-Rad BioPlex 2200. Antitreponemal antibodies were detected in 87% of PNG sera versus -6% of controls (P < .0001). Anti-dsDNA antibodies were detected in 31% of PNG samples, which was significantly higher than in three of the control groups (<10%). The outstanding high rate of antitreponemal antibodies detected in Kitavans possibly represents prior yaws disease. A low prevalence of cardiovascular disease was previously documented in Kitavans and has been attributed, in addition to their diet, to the high prevalence of natural cardioprotective autoantibodies (the IgM-antiphosphorylcholine antibodies) in this population. Treponemal infection has been shown to induce the appearance of antiphosphorylcholine antibodies. These protective autoantibodies may cross-react with the pathogenic anti-dsDNA antibodies. Thus, it is suggested that infection with treponema is associated with the presence of protective as well as pathogenic autoantibodies.
Nora Badawi,
Stig Rønhede,
Stefan Olsson,
Birthe B Kragelund,
Anders H Johnsen,
Ole Stig Jacobsen,
Jens Aamand
Department of Geochemistry, Geological Survey of Denmark and Greenland (GEUS), Østervoldgade 10, DK-1350 Copenhagen K, Denmark.
Phenylurea herbicides are used worldwide, and often pollute surface- and groundwater in concentrations exceeding the limit value for drinking water ( .1 mug l(-1)). Bacteria degrade phenylurea herbicides by successive N-dealkylation to substituted aniline products. Little is known about the corresponding fungal pathways, however. We here report degradation of chlorotoluron, diuron, isoproturon and linuron by the soil fungus Mortierella sp. Gr4. Degradation was fastest with linuron and resulted in successively dealkylated metabolites and 3,4-dichloroaniline. A major new metabolite was detected that has not yet been fully identified. Thin layer chromatography and nuclear magnetic resonance spectroscopy indicate that it is a non-aromatic diol. Degradation of isoproturon, chlorotoluron and diuron involved successive N-demethylation and, in the case of isoproturon and chlorotoluron, additional hydroxylation. A new hydroxylated isoproturon metabolite was detected. The study thus shows that the fungal pathways differ from the bacterial pathways and yield new metabolites of possible environmental concern.
Institute of Biomedical Engineering.
Mice are increasingly used in studies where measuring insulin sensitivity (IS) is a common procedure. Glucose clamp is labor intensive, cannot be used in large numbers of animals, cannot be repeated in the same mouse and has been questioned as a valid tool for IS in mice; thus, the minimal model with 50min-intravenous glucose (IVGTT) data was adapted in mice. However, specific software and particular ability is needed. Aim of this study was to establish a simple procedure for evaluating IS during IVGTT in mice (CSI). IVGTT (n=520) were performed in NMRI and C57BL/6J mice (20-25g). After glucose injection (1 g/kg), 7 samples were collected until 50 min for glucose and insulin measurements, analyzed with minimal model which provided the validated reference IS (SI). By using the regression CSI=alpha1+alpha2xKG/AUCD, IS was calculated in 134 control animals randomly selected (regression CSI vs. SI: r= .66, p< .0001) and yielded alpha1=1.93 and alpha2= .24. KG is the slope of log(glucose5-20) and AUCD is the mean dynamic area under insulin curve in the IVGTT. By keeping fixed alpha1 and alpha2, CSI was validated in 143 control mice (4.7+/- .2 min(-1)microU(-1)ml, virtually identical to SI: 4.7+/- .3, r= .89, p< .0001; and in 123 mice in different conditions: transgenic, addition of neuropeptides, incretins, insulin (CSI: 6. +/- .4 vs. SI: 6.1+/- .4, r= .94, p< .0001). In other 120 animals, CSI revealed its ability to segregate different categories, as SI does. This easily usable formula for calculating CSI overcomes many experimental obstacles and may be a simple alternative to more complex procedures when large numbers of mice or repeated experiments in the same animals are required. Key words: glucose tolerance, insulin resistance, glucose effectiveness, animal model.
Richard David Carr,
Marianne Olholm Larsen,
Maria Sorhede Winzell,
Katarina Jelic,
Ola Lindgren,
Carolyn F Deacon,
Bo Ahren
Merck, Sharp and Dohme A/S.
Glucagon-like 1 peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) regulate islet function after carbohydrate ingestion. Whether incretin hormones are of importance for islet function after ingestion of non-carbohydrate macronutrients is not known. This study therefore examined the integrated incretin and islet hormone responses to ingestion of pure fat (oleic acid; .88 g/kg) or protein (milk and egg protein; 2 g/kg) over 5 hours in healthy men, aged 20-25 years (n=12); plain water ingestion served as control. Both intact (active) and total GLP-1 and GIP levels were determined as was plasma activity of dipeptidyl peptidase-4 (DPP-4). Following water ingestion, glucose, insulin, glucagon, GLP-1 and GIP levels and DPP-4 activity were stable during the 5 hour study period. Both fat and protein ingestion increased insulin, glucagon, GIP and GLP-1 levels without affecting glucose levels or DPP-4 activity. The GLP-1 responses were similar after protein and fat, whereas the early (30 min) GIP response was higher after protein than after fat ingestion (P< .001). This was associated with seven-fold higher insulin and glucagon responses compared to fat ingestion (both P< .001). After protein, the early GIP, but not GLP-1, responses correlated to insulin (r(2)= .86; P= .0001) but not glucagon responses. In contrast, after fat ingestion, GLP-1 and GIP did not correlate to islet hormones. We conclude that whereas protein and fat release both incretin and islet hormones, the early GIP secretion after protein ingestion may be of primary importance to islet hormone secretion. Key words: insulin, glucagon, GLP-1, GIP.
Institutionen för kliniska vetenskaper, Lund. Staffan.Lindeberg@med.lu.se
Institutionen för kliniska vetenskaper, Lund. Staffan.Lindeberg@med.lu.se
Alan A Sneddon,
Fotini Tsofliou,
Claire L Fyfe,
Ian Matheson,
Diane M Jackson,
Graham Horgan,
Maria S Winzell,
Klaus W J Wahle,
Bo Ahren,
Lynda M Williams
1Vascular Health Division, Rowett Research Institute, Aberdeen, UK.
This study aimed to determine the effect of supplementation with conjugated linoleic acids (CLAs) plus n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) on body composition, adiposity, and hormone levels in young and older, lean and obese men. Young (31.4 +/- 3.9 years) lean (BMI, 23.6 +/- 1.5 kg/m(2); n = 13) and obese (BMI, 32.4 +/- 1.9 kg/m(2); n = 12) and older (56.5 +/- 4.6 years) lean (BMI, 23.6 +/- 1.5 kg/m(2); n = 20) and obese (BMI, 32. +/- 1.6 kg/m(2); n = 14) men participated in a double-blind placebo-controlled, randomized crossover study. Subjects received either 6 g/day control fat or 3 g/day CLA (50:50 cis-9, trans-11:trans-10, cis-12) and 3 g/day n-3 LC-PUFA for 12 weeks with a 12-week wash-out period between crossovers. Body composition was assessed by dual-energy X-ray absorptiometry. Fasting adiponectin, leptin, glucose, and insulin concentrations were measured and insulin resistance estimated by homeostasis model assessment for insulin resistance (HOMA-IR). In the younger obese subjects, CLA plus n-3 LC-PUFA supplementation compared with control fat did not result in increased abdominal fat and raised both fat-free mass (2.4%) and adiponectin levels (12%). CLA plus n-3 LC-PUFA showed no significant effects on HOMA-IR in any group but did increase fasting glucose in older obese subjects. In summary, supplementation with CLA plus n-3 LC-PUFA prevents increased abdominal fat mass and raises fat-free mass and adiponectin levels in younger obese individuals without deleteriously affecting insulin sensitivity, whereas these parameters in young and older lean and older obese individuals were unaffected, apart from increased fasting glucose in older obese men.Obesity (2008) doi:10.1038/oby.2008.41.
Research and Development Centre (E.K.S.), Skaraborg Hospital, Skövde, and Institute of Health and Caring Sciences (E.K.S., J.Ö., T.J., F.G.-J.), Sahlgrenska Academy at Göteborg University, Göteborg, Sweden; and Johns Hopkins School of Nursing (F.G.-J.), Baltimore, Maryland, USA.
Little is known about how postmenopausal women with recurrent breast cancer cope with distressing symptoms and which factors predict health-related quality of life (HRQOL). In the present study, 56 consecutively enrolled patients completed questionnaires measuring symptom occurrence, coping capacity, coping efforts, and HRQOL at the time of recurrence. Results from this study illustrate that women with recurrent breast cancer suffer from multiple, concurrent, and interrelated symptoms of illness, anxiety, depression, and fatigue. Highly prevalent symptoms are lack of energy, difficulty sleeping, pain, worrying, problems with sexual interest, feeling sad, and dry mouth. The most frequently occurring symptom is problem with sexual interest, and the most severe symptom is worrying. The most distressing symptom experienced is pain. The majority of the women report 10-23 symptoms. Women who experience multiple symptoms also report higher levels of symptom distress. The experience of distressing symptoms is predicted by coping capacity, and the coping efforts experienced predict HRQOL. Patients with lower coping capacity report higher prevalence of symptoms, experience higher levels of distress, and experience worse perceived health, which in turn may decrease their HRQOL. To help women manage recurrent breast cancer, it is important to use multidimensional measurement to identify, evaluate, and treat distressing symptoms, and not assess single symptoms only. Care must be based upon the awareness of critical factors that exacerbate vulnerability to distress, as well as the ability to adapt to a recurrent breast cancer disease.
Latest similar papers:
Schuyler W. Henderson, M.D., and Michael S. Jellinek, M.D., served as Assistant Editors for this editorial.
In the course of the "Neolithic Revolution", while the warming after the glacial period about 13,000 years ago was starting, the crucial evolution of mankind took place, which has consequences to this day. With the beginning of agriculture and metallurgy a transition from an accidental outlook on life to a deliberate shaping of life set in. A chance from almost egalitarian tribal societies oriented solely towards consumption into production societies organized in a hierarchically complex way was not solely the result of an adaptation to climatic conditions, but also of a positively selecting evolution of the intellect. Following the socially relevant upheavals connected with this, the prerequisites for starting modest prosperity only for a privileged few across millenniums were created. Problems and future prospects of today's global distribution of affluence are discussed.
University of Cincinnati Genome Research Institute, Department of Psychiatry, Obesity Research Center, 2170 East Galbraith Road, Cincinnati, Ohio 45327. tschoemh@ucmail.uc.edu.
Departamento de Nutrição e Dietética, Instituto de Nutrição Josué de Castro, Universidade Federal do Rio de Janeiro-RJ, Brasil. elianerosado@nutricao.ufrj.br
The obesity is a multicausal disease that includes exogenous and endogenous factors. We emphasized the leptin, a hormone produced by adipose tissue, whose receiver is in the hypothalamus. The leptin has been considered important in the development of the obesity, because it influences in the energy intake and expenditure. In the revision one sets out to evaluate the leptin like factor related to the development of the obesity, as well as the influence of diet in the secretion and action of leptin. In the human obesity, the deficiency of functional leptin is rare, nevertheless, can exist leptin resistance. After the loss weight it happens reduction in the leptin levels, which can be in the recovery of body weight. The leptin is regulated by food intake and their circulating levels and potential of action are associated with content of macronutrients of the diet and the body composition individually. Nevertheless, studies demonstrated the high and the low food intake can influence in the leptin secretion, independent of the effect on adiposity. In addition, the fat of diet presents important effect in secretion and action of leptin. Also the zinc deficiency has been associated with the reduced levels of leptin. Several experimental studies have been made to evaluate the effect of the administration of leptin in treatment of obesity, by means of injections, inhalation or more active forms of leptin. Nevertheless, we need similar studies with humans. Is important the development of studies that associate the environmental factors, particularly the diet, with regulation of serum levels and action of leptin in humans.
In this investigation shown the influence of traditional hypocaloric diet on concentration of leptin level and leptin receptor in type 2 diabetic patients. Our results show that diet therapy improves metabolic control, and as a result of a diet were normoglucaemia and decrease of leptin and leptin receptor level in type 2 diabetic patients.
Tommy Jonsson,
Bo Ahren,
Giovanni Pacini,
Frank Sundler,
Nils Wierup,
Stig Steen,
Trygve Sjoberg,
Martin Ugander,
Johan Frostegard,
Leif Goransson,
Staffan Lindeberg
ABSTRACT: BACKGROUND: A Paleolithic diet has been suggested to be more in concordance with human evolutionary legacy than a cereal based diet. This might explain the lower incidence among hunter-gatherers of diseases of affluence such as type 2 diabetes, obesity and cardiovascular disease. The aim of this study was to experimentally study the long-term effect of a Paleolithic diet on risk factors for these diseases in domestic pigs. We examined glucose tolerance, post-challenge insulin response, plasma C-reactive protein and blood pressure after 15 months on Paleolithic diet in comparison with a cereal based swine feed. METHODS: Upon weaning twenty-four piglets were randomly allocated either to cereal based swine feed (Cereal group) or cereal free Paleolithic diet consisting of vegetables, fruit, meat and a small amount of tubers (Paleolithic group). At 17 months of age an intravenous glucose tolerance test was performed and pancreas specimens were collected for immunohistochemistry. Group comparisons of continuous variables were made by use of the t-test. P< .05 was chosen for statistical significance. Simple and multivariate correlations were evaluated by use of linear regression analysis. RESULTS: At the end of the study the Paleolithic group weighed 22% less and had 43% lower subcutaneous fat thickness at mid sternum. No significant difference was seen in fasting glucose between groups. Dynamic insulin sensitivity was significantly higher (p= .004) and the insulin response was significantly lower in the Paleolithic group (p= .001). The geometric mean of C-reactive protein was 82% lower (p= .0007) and intra-arterial diastolic blood pressure was 13% lower in the Paleolithic group (p= .007). In evaluations of multivariate correlations, diet emerged as the strongest explanatory variable for the variations in dynamic insulin sensitivity, insulin response, C-reactive protein and diastolic blood pressure when compared to other relevant variables such as weight and subcutaneous fat thickness at mid sternum. There was no obvious immunohistochemical difference in pancreatic islets between the groups, but leukocytes were clearly more frequent in sampled pancreas from the Cereal group. CONCLUSIONS: This study in domestic pigs suggests that a Paleolithic diet conferred higher insulin sensitivity, lower C-reactive protein and lower blood pressure when compared to a cereal based diet.
