Caroline Mellberg

Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: a 2-year randomized trial

Background/Objectives:Short-term studies have suggested beneficial effects of a Palaeolithic-type diet (PD) on body weight and metabolic balance. We now report the long-term effects of a PD on anthropometric measurements and metabolic balance in obese postmenopausal women, in comparison with a diet according to the Nordic Nutrition Recommendations (NNR).Subjects/Methods:Seventy obese postmenopausal women (mean age 60 years, body mass index 33 kg/m2) were assigned to an ad libitum PD or NNR diet in a 2-year randomized controlled trial. The primary outcome was change in fat mass as measured by dual-energy X-ray absorptiometry.Results:Both groups significantly decreased total fat mass at 6 months (−6.5 and−2.6 kg) and 24 months (−4.6 and−2.9 kg), with a more pronounced fat loss in the PD group at 6 months (P<0.001) but not at 24 months (P=0.095). Waist circumference and sagittal diameter also decreased in both the groups, with a more pronounced decrease in the PD group at 6 months (−11.1 vs−5.8 cm, P=0.001 and−3.7 vs−2.0 cm, P<0.001, respectively). Triglyceride levels decreased significantly more at 6 and 24 months in the PD group than in the NNR group (P<0.001 and P=0.004). Nitrogen excretion did not differ between the groups.Conclusions:A PD has greater beneficial effects vs an NNR diet regarding fat mass, abdominal obesity and triglyceride levels in obese postmenopausal women; effects not sustained for anthropometric measurements at 24 months. Adherence to protein intake was poor in the PD group. The long-term consequences of these changes remain to be studied.

A Palaeolithic-type diet causes strong tissue-specific effects on ectopic fat deposition in obese postmenopausal women

Ectopic fat accumulation in liver and skeletal muscle may be an essential link between abdominal obesity, insulin resistance and increased risk of cardiovascular disease after menopause. We hypothesized that a diet containing a relatively high content of protein and unsaturated fat [mainly monounsaturated fatty acids (MUFAs)] but limited carbohydrates and saturated fat would reduce lipid content in liver and muscle and increase insulin sensitivity in postmenopausal women.

Profound cardiac conduction delay predicts mortality in myotonic dystrophy type 1

Abstract.  Mörner S, Lindqvist P, Mellberg C, Olofsson B‐O, Backman C, Henein M, Lundblad D, Forsberg H (Umeå University Hospital, Umeå; Umeå University, Umeå; Sunderby Hospital, Luleå; Sweden). Profound cardiac conduction delay predicts mortality in myotonic dystrophy type 1. J Intern Med 2010; 268:59–65.

Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention.

Background/Objectives:Our objective was to investigate changes in liver fat and insulin sensitivity during a 2-year diet intervention. An ad libitum Paleolithic diet (PD) was compared with a conventional low-fat diet (LFD).Subjects/Methods:Seventy healthy, obese, postmenopausal women were randomized to either a PD or a conventional LFD. Diet intakes were ad libitum. Liver fat was measured with proton magnetic resonance spectroscopy. Insulin sensitivity was evaluated with oral glucose tolerance tests and calculated as homeostasis model assessment-insulin resistance (HOMA-IR)/liver insulin resistance (Liver IR) index for hepatic insulin sensitivity and oral glucose insulin sensitivity (OGIS)/Matsuda for peripheral insulin sensitivity. All measurements were performed at 0, 6 and 24 months. Forty-one women completed the examinations for liver fat and were included.Results:Liver fat decreased after 6 months by 64% (95% confidence interval: 54–74%) in the PD group and by 43% (27–59%) in the LFD group (P<0.01 for difference between groups). After 24 months, liver fat decreased 50% (25–75%) in the PD group and 49% (27–71%) in the LFD group. Weight reduction between baseline and 6 months was correlated to liver fat improvement in the LFD group (rs=0.66, P<0.01) but not in the PD group (rs=0.07, P=0.75). Hepatic insulin sensitivity improved during the first 6 months in the PD group (P<0.001 for Liver IR index and HOMA-IR), but deteriorated between 6 and 24 months without association with liver fat changes.Conclusions:A PD with ad libitum intake had a significant and persistent effect on liver fat and differed significantly from a conventional LFD at 6 months. This difference may be due to food quality, for example, a higher content of mono- and polyunsaturated fatty acids in the PD. Changes in liver fat did not associate with alterations in insulin sensitivity.

Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women.

Background/Objectives:Tissue-specific glucocorticoid metabolism is altered in obesity, and may increase cardiovascular risk. This dysregulation is normalized by short-term calorie restriction and weight loss, an effect that varies with dietary macronutrient composition. However, tissue-specific glucocorticoid metabolism has not been studied during long-term (>6 months) dietary interventions. Therefore our aim was to test whether long-term dietary interventions, either a paleolithic-type diet (PD) or a diet according to Nordic nutrition recommendations (NNR) could normalize tissue-specific glucocorticoid metabolism in overweight and obese women.Subjects/Methods:Forty-nine overweight/obese postmenopausal women were randomized to a paleolithic diet or a diet according to NNR for 24 months. At baseline, 6 and 24 months anthropometric measurements, insulin sensitivity, excretion of urinary glucocorticoid metabolites in 24-hour collections, conversion of orally administered cortisone to plasma cortisol and transcript levels of 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) in subcutaneous adipose tissue were studied.Results:Both diet groups achieved significant and sustained weight loss. Weight loss with the PD was greater than on NNR diet after 6 months (P<0.001) but similar at 24 months. Urinary measurement of 5α-reductase activity was increased after 24 months in both groups compared with baseline (P<0.001). Subcutaneous adipose tissue 11βHSD1 gene expression decreased at 6 and 24 months in both diet groups (P=0.036). Consistent with increased liver 11βHSD1, conversion of oral cortisone to cortisol increased at 6 months (P=0.023) but was unchanged compared with baseline by 24 months.Conclusions:Long-term weight loss in postmenopausal women has tissue-specific and time-dependent effects on glucocorticoid metabolism. This may alter local-tissue cortisol exposure contributing to improved metabolic function during weight loss.

Left ventricular remodelling changes without concomitant loss of myocardial fat after long-term dietary intervention.

BACKGROUND Accumulation of myocardial triglycerides (MTG) is associated with impaired left ventricular (LV) remodelling and function in obese and diabetic subjects. The role of MTG accumulation in development of heart failure in this group of patients is unknown. Short-term studies suggest that diets that lead to weight loss could mobilize MTG, with a favourable effect on cardiac remodelling. In a 24-month, randomized, investigator-blinded study, we assessed the effect of two different diets and subsequent weight loss on cardiac function and MTG in postmenopausal women. METHODS Sixty-eight healthy postmenopausal women with body mass index [BMI] ≥27kg/m(2) were randomized to an ad libitum Palaeolithic diet (PD) or a Nordic Nutrition Recommendation (NNR) diet for 24months. Morphology, cardiac function, and MTG levels were measured using magnetic resonance (MR) scanning, including proton spectroscopy at baseline and 6 and 24months. RESULTS Despite mean weight losses of 4.9 (1.0) kg (NNR) and 7.8 (1.1) kg (PD), the MTG content did not change over time (p=0.98 in the NNR and p=0.11 in the PD group at 24months). Reduced left ventricular mass was observed in both diet groups over 24months. Blood pressure was reduced at 6months, but returned to baseline levels at 24months. End diastolic volume, stroke volume, and cardiac output decreased over time. No differences between diet groups were observed. CONCLUSIONS Diet intervention and moderate weight loss over 24months improved LV remodelling but did not alter MTG levels in overweight/obese postmenopausal women.

Plasma metabolomic response to postmenopausal weight loss induced by different diets

BackgroundMenopause is associated with increased abdominal fat and increased risk of developing diabetes and cardiovascular disease.ObjectivesThe present study evaluated the plasma metabolic response in relation to insulin sensitivity after weight loss via diet intervention.MethodsThis work includes two studies; i) Ten women on a 5 weeks Paleolithic-type diet (PD, 30 energy percent (E%) protein, 40 E% fat, 30 E% carbohydrates), ii) 55 women on 6 months of either PD or Nordic Nutrition Recommendations diet (NNR, 15 E% protein, 30 E% fat, and 55 E% carbohydrates). Plasma metabolic profiles were acquired at baseline and post diet using gas chromatography time-of-flight/mass spectrometry and investigated in relation to insulin sensitivity using multivariate bioinformatics.ResultsBoth the PD and NNR diet resulted in significant weight loss, reduced waist circumference, improved serum lipid profiles, and improved insulin sensitivity. We detected a baseline metabolic profile that correlated significantly with insulin sensitivity, and of which components increased significantly in the PD group compared to NNR. Specifically, a significant increase in myo-inositol (MI), a second messenger of insulin action, and β-hydroxybutyric acid (β-HB) increased while dihomo-gamma-linoleic acid (DGLA) decreased in PD compared to NNR, which correlated with improved insulin sensitivity. We also detected a significant decrease in tyrosine and tryptophan, potential markers of insulin resistance when elevated in the circulation, with the PD but not the NNR.ConclusionsUsing metabolomics, we detected changes in the plasma metabolite profiles associated with weight loss in postmenopausal women by different diets. The metabolic profiles following 6 months of PD were linked to beneficial effects on insulin sensitivity compared to NNR.Graphical Abstract

A Paleolithic-type diet results in iodine deficiency: a 2-year randomized trial in postmenopausal obese women

Background/Objectives:Different diets are used for weight loss. A Paleolithic-type diet (PD) has beneficial metabolic effects, but two of the largest iodine sources, table salt and dairy products, are excluded. The objectives of this study were to compare 24-h urinary iodine concentration (24-UIC) in subjects on PD with 24-UIC in subjects on a diet according to the Nordic Nutrition Recommendations (NNR) and to study if PD results in a higher risk of developing iodine deficiency (ID), than NNR diet.Subjects/Methods:A 2-year prospective randomized trial in a tertiary referral center where healthy postmenopausal overweight or obese women were randomized to either PD (n=35) or NNR diet (n=35). Dietary iodine intake, 24-UIC, 24-h urinary iodine excretion (24-UIE), free thyroxin (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) were measured at baseline, 6 and 24 months. Completeness of urine sampling was monitored by para-aminobenzoic acid and salt intake by urinary sodium.Results:At baseline, median 24-UIC (71.0 μg/l) and 24-UIE (134.0 μg/d) were similar in the PD and NNR groups. After 6 months, 24-UIC had decreased to 36.0 μg/l (P=0.001) and 24-UIE to 77.0 μg/d (P=0.001) in the PD group; in the NNR group, levels were unaltered. FT4, TSH and FT3 were similar in both groups, except for FT3 at 6 months being lower in PD than in NNR group.Conclusions:A PD results in a higher risk of developing ID, than a diet according to the NNR. Therefore, we suggest iodine supplementation should be considered when on a PD.

Attenuated Low-Grade Inflammation Following Long-Term Dietary Intervention in Postmenopausal Women with Obesity

Abdominal fat accumulation after menopause is associated with low‐grade inflammation and increased risk of metabolic disorders. Effective long‐term lifestyle treatment is therefore needed.