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Effect of an energy-restricted, high-protein, low-fat diet relative to a conventional high-carbohydrate, low-fat diet on weight loss, body composition, nutritional status, and markers of cardiovascular health in obese women

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Limited evidence suggests that a higher ratio of protein to carbohydrate during weight loss has metabolic advantages. The objective was to evaluate the effects of a diet with a high ratio of protein to carbohydrate during weight loss on body composition, cardiovascular disease risk, nutritional status, and markers of bone turnover and renal function in overweight women. The subjects were randomly assigned to 1 of 2 isocaloric 5600-kJ dietary interventions for 12 wk according to a parallel design: a high-protein (HP) or a high-carbohydrate (HC) diet. One hundred women with a mean (+/-SD) body mass index (in kg/m(2)) of 32 +/- 6 and age of 49 +/- 9 y completed the study. Weight loss was 7.3 +/- 0.3 kg with both diets. Subjects with high serum triacylglycerol (>1.5 mmol/L) lost more fat mass with the HP than with the HC diet (x +/- SEM: 6.4 +/- 0.7 and 3.4 +/- 0.7 kg, respectively; P = 0.035) and had a greater decrease in triacylglycerol concentrations with the HP (-0.59 +/- 0.19 mmol/L) than with the HC (-0.03 +/- 0.04 mmol/L) diet (P = 0.023 for diet x triacylglycerol interaction). Triacylglycerol concentrations decreased more with the HP (0.30 +/- 0.10 mmol/L) than with the HC (0.10 +/- 0.06 mmol/L) diet (P = 0.007). Fasting LDL-cholesterol, HDL-cholesterol, glucose, insulin, free fatty acid, and C-reactive protein concentrations decreased with weight loss. Serum vitamin B-12 increased 9% with the HP diet and decreased 13% with the HC diet (P < 0.0001 between diets). Folate and vitamin B-6 increased with both diets; homocysteine did not change significantly. Bone turnover markers increased 8-12% and calcium excretion decreased by 0.8 mmol/d (P < 0.01). Creatinine clearance decreased from 82 +/- 3.3 to 75 +/- 3.0 mL/min (P = 0.002). An energy-restricted, high-protein, low-fat diet provides nutritional and metabolic benefits that are equal to and sometimes greater than those observed with a high-carbohydrate diet.
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Effect of an energy-restricted, high-protein, low-fat diet relative to a
conventional high-carbohydrate, low-fat diet on weight loss, body
composition, nutritional status, and markers of cardiovascular health
in obese women
1–3
Manny Noakes, Jennifer B Keogh, Paul R Foster, and Peter M Clifton
ABSTRACT
Background: Limited evidence suggests that a higher ratio of pro-
tein to carbohydrate during weight loss has metabolic advantages.
Objective: The objective was to evaluate the effects of a diet with a
high ratio of protein to carbohydrate during weight loss on body
composition, cardiovascular disease risk, nutritional status, and
markers of bone turnover and renal function in overweight women.
Design: The subjects were randomly assigned to 1 of 2 isocaloric
5600-kJ dietary interventions for 12 wk according to a parallel de-
sign: a high-protein (HP) or a high-carbohydrate (HC) diet.
Results: One hundred women with a mean (SD) body mass index
(in kg/m
2
)of32 6 and age of 49 9 y completed the study. Weight
loss was 7.3 0.3 kg with both diets. Subjects with high serum
triacylglycerol (1.5 mmol/L) lost more fat mass with the HP than
with the HC diet (x SEM: 6.4 0.7 and 3.4 0.7 kg, respectively;
P ҃ 0.035) and had a greater decrease in triacylglycerol concen-
trations with the HP (Ҁ0.59 0.19 mmol/L) than with the HC
(Ҁ0.03 0.04 mmol/L) diet (P ҃ 0.023 for diet ҂ triacylglycerol
interaction). Triacylglycerol concentrations decreased more with the
HP (0.30 0.10 mmol/L) than with the HC (0.10 0.06 mmol/L)
diet (P ҃ 0.007). Fasting LDL-cholesterol, HDL-cholesterol, glu-
cose, insulin, free fatty acid, and C-reactive protein concentrations
decreased with weight loss. Serum vitamin B-12 increased 9% with
the HP diet and decreased 13% with the HC diet (P 0.0001
between diets). Folate and vitamin B-6 increased with both diets;
homocysteine did not change significantly. Bone turnover markers
increased 8 –12% and calcium excretion decreased by 0.8 mmol/d
(P 0.01). Creatinine clearance decreased from 82 3.3 to 75 3.0
mL/min (P ҃ 0.002).
Conclusion: An energy-restricted, high-protein, low-fat diet pro-
vides nutritional and metabolic benefits that are equal to and some-
times greater than those observed with a high-carbohydrate
diet. Am J Clin Nutr 2005;81:1298–306.
KEY WORDS Weight loss, diet composition, high-protein
diet, lipids, dual-energy X-ray absorptiometry, bone turnover, nu-
tritional status
INTRODUCTION
Obesity is a major health concern because it is implicated in the
development of many chronic diseases. Strategies recommended
for weight control have generally recommended the adoption of
low-fat dietary patterns, which facilitate energy restriction and
cardiovascular disease risk reduction. However, studies of the
role of a high dietary ratio of protein to carbohydrate in enhancing
weight loss and disease risk management have emerged along
with an increasing public interest in weight control. From an
epidemiologic perspective, a positive health benefit from a high
protein intake was observed in the Nurses’ Health Study, which
found a 26% lower rate of cardiovascular disease in those women
in the highest protein intake group than in those in the lowest
protein intake group (1). Clinical intervention studies have pro-
vided sound evidence that an ad libitum high-protein diet from
mixed sources in free-living overweight people increases the
amount of weight lost in a 6-mo weight-loss program (by 3.8 kg)
compared with a high-carbohydrate diet by enhancing satiety (2).
Furthermore, weight-loss studies in overweight women have
shown that diets with a high ratio of protein to carbohydrate have
positive effects on markers of disease risk, including body com-
position, blood lipids, and glucose homeostasis, and that these
benefits may be mediated partly by the effect of protein on satiety
and by a lower glycemic load because of a lower carbohydrate
intake (3, 4). A higher protein intake during weight loss may also
prevent some of the inevitable loss of lean body mass and, thus,
may enhance insulin sensitivity (5, 6), although this has not been
observed at very low energy intakes (7). In 2 studies in over-
weight men and women, with either insulin resistance or type 2
diabetes, we showed that a high-protein weight-loss diet (28
30% of energy from protein) from mixed sources enhances fat
loss by 1–2 kg over 12 wk, particularly in women, compared with
an isocaloric high-carbohydrate weight-loss diet (8, 9). It is
known that different protein sources have different effects on the
release of insulin (10, 11), and this may be important to the
mechanism of action of both the enhanced satiety (Latner and
Schwartz 1999) and the differential fat loss. However, foods and
dietary patterns high in protein may vary in saturated fat and
1
From CSIRO Health Sciences and Nutrition, Adelaide, Australia.
2
Supported by a Medical Research grant from Meat and Livestock Aus-
tralia.
3
Address reprint requests to M Noakes, PO Box 10041, Adelaide BC,
South Australia, Australia 5000. E-mail: manny.noakes@csiro.au.
Received April 5, 2004.
Accepted for publication January 10, 2005.
1298 Am J Clin Nutr 2005;81:1298 –306. Printed in USA. © 2005 American Society for Clinical Nutrition
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nutritional composition, and concerns have been raised regard-
ing the effect of high-protein diets on serum lipids and subse-
quent cardiovascular disease risk. Evidence also exists that high-
protein diets enhance calcium excretion and increase bone loss,
which particularly needs clarification (12).
The purpose of the study was to determine the effect of reduced
caloric intake, associated with higher dietary protein from low
saturated fat sources compared with a high-carbohydrate diet, on
weight loss, body composition, cardiovascular disease risk, nu-
tritional status, and markers of bone turnover in overweight and
obese women. We hypothesized as our primary outcome that the
high-protein diet would enhance fat loss and minimize lean mass
loss compared with the high-carbohydrate diet.
SUBJECTS AND METHODS
Subjects
Women were recruited by public advertisement. They were
screened by questionnaire and verbally to assess their perceived
ability to comply with an energy-restricted dietary regimen. To
be eligible for the study, subjects had to be females between 20 and
65 y of age, have a body mass index (BMI; in kg/m
2
) between 27 and
40, and have no history of metabolic disease or type 1 or type 2
diabetes. One hundred and nineteen women met the selection cri-
teria and were randomly assigned to treatment (Figure 1).
All subjects gave written informed consent to participate in the
study, which was approved by the Human Ethics Committee of
the Commonwealth Scientific and Industrial Research Organi-
zation, Health Sciences and Nutrition, Adelaide, Australia. Nine-
teen women withdrew from the study before completion, 6 in the
high-protein group and 13 in the high-carbohydrate group. Sub-
ject characteristics were not significantly different between diet
groups at baseline (Table 1).
Study design
The subjects were randomly assigned to 1 of 2 isocaloric
5600-kJ dietary interventions for 12 wk according to a parallel
design: 1) a high-protein, low-saturated-fat dietary pattern [HP
group; 34% of energy from protein, 20% from fat (10% from
saturated fat) and 46% from carbohydrate] and 2) a high-
carbohydrate, low-saturated-fat dietary pattern [HC group; 17%
of energy from protein, 20% from fat (10% from saturated fat),
and 64% from carbohydrate].
The subjects attended individual consultations with 2 dieti-
tians, alternately every 4 wk, throughout the study for instruction
on the dietary requirements and methods of recording food intake
and for the assessment of compliance. The subjects were issued
with digital kitchen scales to weigh food and were advised to
consume 2 cups of low-carbohydrate vegetables per day; they
were advised to not eat potato, sweet potato, and avocado. A
range of additional low-energy foods was allowed. Two standard
servings of alcohol were permitted per week. Eating at restau-
rants was limited to once every 2 wk. Every 2 wk, the subjects
attended the Clinical Research Unit and were supplied with foods
consistent with their allocated diet to encourage compliance.
Each allocation provided 60% of the projected total energy
intake for 7 d and was isocaloric for both groups.
FIGURE 1. Schematic representation of randomization.
TABLE 1
Subject characteristics at baseline
1
HP group (n ҃ 52) HC group (n ҃ 48)
Weight (kg) 87 12 86 12
Age (y) 50 10 49 9
BMI (kg/m
2
)32 633 4
1
All values are x SD. HP, high protein; HC, high carbohydrate. There
were no significant differences between groups by two-tailed unpaired t test.
EFFECT OF A LOW-FAT, HIGH-PROTEIN DIET 1299
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The foods prescribed to obtain the planned dietary intakes in
both diet groups are outlined in Table 2. The total energy content
of each diet was initially 5600 kJ, but was adjusted upward for
very active subjects so that weight loss would be 1 kg/wk for
the first 2–3 wk. The fiber content and fatty acid profile were
planned to be the same between diets. Key foods were supplied
to the subjects, and the energy content of the foods provided was
the same for both diet groups. Specifically, lean red meat was
provided in 200-g portion packs and lunch meat, chicken, or fish
in 100-g portion packs for 6 meals/wk for the HP group; 80-g
packs of chicken and pork plus pasta, rice, biscuits, and whole-
meal bread were provided to the HC group. To simulate a quasi
ad libitum approach, we advised the HP group that it was com-
pulsory to eat 200 g red meat plus 100 g lunch meat, chicken, or
fish daily; the other food items could be consumed according to
appetite but not to exceed the amounts specified. Similarly for the
HC group, we advised that 80 g chicken or pork plus the bread
needed to be consumed daily, and this was isocaloric with the
meat component in the HP diet. Checklists of all foods consumed
were completed daily, and 3-d weighed food records were ana-
lyzed in each 2-wk period. The subjects were interviewed by a
dietitian individually every 4 wk. Two qualified dietitians pro-
vided the dietary counseling and conducted the nutrient analyses.
Both dietitians were trained to provide consistent information to
the subjects and on the methods for analysis. Advice on physical
activity was also consistent with a recommendation to increase
physical activity to 30 min 3 times/wk and to document these
occasions in their daily checklist.
Food-preparation sessions specific to the diet protocol were
conducted by a home economist every 4 wk for each diet group,
and recipes were provided. The composition of the diets con-
sumed by the subjects and their compliance throughout the study
were assessed through 3-d dietary food records that were com-
pleted every 4 wk and dietary checklists that were completed
daily. Energy and macronutrient intakes were calculated by us-
ing Diet 4 nutritional calculation software (Xyris Software,
Highgate Hill, Australia), which is based on Australian food-
composition tables and data from food manufacturers.
Body weight and composition
Subjects were weighed every 14 d (model AMZ14; Mercury
Digital Scales, Japan) while wearing light clothing and no shoes
and after fasting overnight. Height was measured with a stadi-
ometer (Seca, Hamburg, Germany) at week 0. BMI was calcu-
lated as weight (kg)/height squared (m). Dual-energy X-ray ab-
sorptiometry (Norland Medical Systems Inc, Fort Atkinson, WI)
was performed at weeks 0 and 12 (Royal Adelaide Hospital,
Adelaide, Australia).
Urinalysis
Collection of total 24-h urine output commenced at 0700 (not
including the first morning void) on the day before the subjects
attended the research clinic and was completed at 0700 on the day
of clinic attendance (including the first morning void) at weeks 0
and 12. Urine samples were measured at the Institute of Medical
and Veterinary Science (Adelaide, South Australia) for creati-
nine, urea, calcium phosphate, and sodium by using proprietary
techniques with the Olympus AU5400 chemistry analyzer (To-
kyo, Japan). Deoxypyridinoline and pyridinoline were measured
by using HPLC (13) and expressed per mmol creatinine.
Biochemistry
Fasting blood samples were collected at weeks 0, 4, 8, and 12
in tubes containing either no additives [for the measurement of
lipids, insulin, and C-reactive protein (CRP)] or sodium fluoride
EDTA for the measurement of glucose. Plasma or serum was
isolated by centrifugation at 2000 ҂ g for 10 min at 5 °C (model
GS-6R centrifuge; Beckman, Fullerton, CA) and frozen at
Ҁ20 °C. Biochemical assays were performed in a single assay at
the completion of the study. Plasma glucose and serum total
cholesterol and triacylglycerol concentrations were measured
with a Cobas-Bio centrifugal analyzer (Roche Diagnostica,
Basel, Switzerland) with the use of enzymatic kits (Hoffmann-La
Roche Diagnostica, Basel, Switzerland) and control sera. Serum
HDL-cholesterol concentrations were measured with a Cobas-
Bio analyzer after precipitation of LDL and VLDL cholesterol
with polyethylene glycol 6000 solution. A modified Friedewald
equation was used to calculate LDL cholesterol (14). Insulin was
measured in duplicate with a radioimmunoassay kit (Pharmacia
& Upjohn Diagnostics AB, Uppsala, Sweden). CRP was mea-
sured with an enzymatic kit (Roche, Indianapolis, IN) on a Hi-
tachi auto analyzer (Roche). Osteocalcin was measured with an
immunometric assay (catalogue no. LKOC1) on an Immulite
Analyzer (Diagnostics Products Corp, Los Angeles, CA).
TABLE 2
Prescriptive food composition of the test diets
1
HP diet HC diet
Cereal 25 g bran cereal ѿ 15 g wheat-flake breakfast biscuit 40 g wheat-flake breakfast biscuit
Milk 250 mL/d (1% fat) 250 mL/d (1% fat)
Low-fat yogurt 200 g Nil
Lean meat, poultry, or fish 200 g lean beef or lamb 6 times/wk ѿ extra 100 g
other protein food daily (lunch)
80 g chicken, pork, or fish (6 times/wk)
ѿ red meat 1 time/wk
Fresh fruit 300 g 450 g
Pasta, rice Nil 120 g cooked (6 times/wk)
Salad 100 g 100 g
Vegetables 400 g 400 g
Canola oil 15 g 15 g
Whole-grain bread 70 g 105 g
Biscuits Nil 2 shortbread biscuits
Wine or equivalent (optional) 300 mL/wk 300 mL/wk
1
HP, high protein; HC, high carbohydrate.
1300 NOAKES ET AL
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Homocysteine, iron, ferritin, folate, vitamin B-6, and vitamin
B-12 were measured at weeks 0 and 12 in a certified commercial
laboratory (Institute of Medical and Veterinary Science, Ad-
elaide, South Australia).
Statistical analysis
All subjects who completed the study were included in the data
analysis, independent of reported dietary compliance, as indi-
cated by food records, weight loss, and urinary urea excretion
relative to creatinine. The statistical analysis was performed with
the use of SPSS 11.0 for WINDOWS (SPSS Inc, Chicago, IL). A
univariate analysis of variance was used to assess differences
between treatment and triacylglycerol status at baseline and to
assess changes in weight and body-composition variables. Di-
etary data were analyzed by using an unpaired t test. Univariate
analysis using the study endpoints, with baseline variable as a
covariate, was used to assess the effects of diet (ie, HP or HC).
Analysis of variance with repeated measures was also used to
determine the effects of time, diet (within-subject factors), and
triacylglycerol status (between-subject factors) and interaction
effects. Data were reanalyzed with baseline BMI as a covariate.
If an interaction was noted, a post hoc subgroup analysis on the
differences was performed by using Tukey’s test. Differences
were considered significant if P 0.05. All data except baseline
characteristics are presented as means SEMs.
RESULTS
Dietary intakes
The self-reported composition of the study diets consumed
during the 3-mo study period is presented in Table 3. There were
no significant differences in total energy, alcohol, and dietary
fiber intakes between the diet groups. Total, saturated, and mono-
unsaturated fat intakes were significantly lower in the HC group,
as was the dietary cholesterol intake. Intakes of the micronutri-
ents thiamine, riboflavin, niacin equivalents, calcium, and iron
were significantly higher in the HP group.
Weight and fat loss
The subjects that dropped out were aged 37 8 y, which was
significantly younger than those who completed the study (P
0.001), but BMI was not significantly different between groups
(P ҃ 0.196). When we undertook an intention-to-treat analysis,
with baseline weight carried forward for dropouts, there was a
significant main effect of diet for weight loss (HP diet: 6.8 3.9
kg; HC diet: 5.4 4.3 kg; P ҃ 0.041). When the analysis was
carried out by using the last weight carried forward for dropouts,
the diet effect was weakened (HP diet: 7.0 3 kg; HC diet:
5.8 4.0 kg; P ҃ 0.066). However, we believe that a “compl-
eters” analysis was a more conservative and appropriate assess-
ment of our data because this was a controlled clinical trial to
examine the metabolic effects of dietary composition. The sub-
jects who completed the 12-wk trial (n ҃ 100) had a mean weight
loss of 7.6 0.4 kg with the HP diet (n ҃ 52) and 6.9 0.5 kg
with the HC diet (n ҃ 48); these values were not significantly
different from each other (P ҃ 0.29). There were 84 subjects with
weight losses 4 kg. However, there was no statistically signif-
icant difference in weight loss or in the number of subjects
achieving 4 kg weight loss by diet. When a subgroup analysis
was conducted, there was a significant interaction with diet and
weight loss according to triacylglycerol status (P ҃ 0.032). Tri-
acylglycerol status was categorized about the median of 1.5
mmol/L.
Weight loss was 25% greater with the HP diet in subjects
with a triacylglycerol concentration 1.5 mmol/L (P ҃ 0.005),
whereas there was no differential effect of diet in women with a
low triacylglycerol concentration (Table 4).
Similarly, the DXA data showed no overall effect of diet
composition on total fat loss (P ҃ 0.16; Table 5), but a signifi-
cant interaction was observed with diet and triacylglycerol status
on total (P ҃ 0.019) and midriff (P ҃ 0.03) fat. In women with
high triacylglycerol concentrations, the total fat loss was 6.4
0.7 kg in the HP group and 3.4 0.7 kg in the HC group (P ҃
0.035 for diet difference; Figure 2). The amount of weight lost
specifically from the midriff area in the HP group was twice that
in the HC group, but the difference was not statistically signifi-
cant by post hoc analysis across the 4 groups (1.0 0.2 kg
compared with 0.5 0.1 kg; P ҃ 0.12).
Serum and urinary urea, creatinine, and creatinine
clearance
The urea-creatinine ratio in urine as well as serum urea were
both significantly different by diet (P ҃ 0.003 and P 0.001,
respectively; Table 6). Creatinine clearance decreased with
weight loss, from 82 3.3 75 3.0 mL/min (8%; P ҃ 0.002),
with no significant difference between the diets (P ҃ 0.346).
There was no significant change in serum creatinine (74.0 0.9
mol/L at baseline compared with 75.4 0.8
mol/L at week
12); therefore, the difference was due to the amount of creatinine
excreted in the urine—from 8.9 0.32 to 8.1 0.21 mmol/d.
There was no correlation between weight loss and change in
creatinine clearance or creatinine excretion. However, adjust-
ment for the change in weight rendered the change in clearance
TABLE 3
Reported dietary intake data assessed by weighed food records
1
HP diet
(n ҃ 52)
HC diet
(n ҃ 47) P
2
Energy (kJ) 5310 55.5
3
5219 78.6 NS
Protein (% of energy) 31.3 0.24 17.8 0.21 0.001
Fat (% of energy) 22.1 0.40 20.1 0.52 0.003
Carbohydrate (% of
energy)
44.2 0.42 60.8 0.58 0.000
Alcohol (% of energy) 1.1 0.24 1.1 0.26 NS
Fiber (g) 27.6 0.58 26.1 0.58 NS
Cholesterol (mg) 216 4.8 78 4.6 0.001
Saturated fat (% of energy) 5.4 0.17 4.6 0.23 0.003
Monounsaturated fat (% of
energy)
9.4 0.20 8.3 0.26 0.001
Polyunsaturated fat (% of
energy)
4.7 0.11 4.7 0.14 NS
Vitamin A equivalent (
g) 1109 53.9 1149 48.4 NS
Vitamin C (mg) 111 4.6 122 7.0 NS
Thiamine (mg) 1.6 0.02 1.4 0.03 0.001
Riboflavin (mg) 2.6 0.04 1.5 0.03 0.001
Niacin equivalent (mg) 48.0 0.43 26.9 0.42 0.001
Calcium (mg) 777 14.7 594 9.8 0.001
Iron (mg) 14.8 0.20 9.6 0.22 0.001
1
HP, high protein; HC, high carbohydrate.
2
Unpaired two-tailed t test between dietary treatments.
3
x SEM over 9 d (all such values).
EFFECT OF A LOW-FAT, HIGH-PROTEIN DIET 1301
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insignificant (P ҃ 0.621), ie, the change in calculated creatinine
clearance was due to the weight change and not to a change in
renal function.
Lipids, glucose, insulin, fatty acids, and C-reactive
protein
There was no significant effect of diet composition on LDL-
cholesterol, HDL-cholesterol, and glucose concentrations (Ta-
ble 7). LDL cholesterol decreased overall by 6%, HDL choles-
terol decreased by 7%, and glucose concentrations decreased by
4% with both diets. Diet composition affected the decrease in
triacylglycerols, which decreased by 8% with the HC diet and by
22% with the HP diet (P ҃ 0.007). Because subjects with high
triacylglycerol concentrations may be more responsive to factors
that alter triacylglycerols, we reanalyzed the data according to
triacylglycerols status (above or below the median of 1.5 mmol/
L). There was a diet ҂ triacylglycerol status interaction for tri-
acylglycerol (P ҃ 0.023). In the women with a high triacylglyc-
erol concentration, the HP diet lowered triacylglycerols
TABLE 4
Interaction between diet and triacylglycerol (TG) status for weight loss
1
Diet and TG status TG concentration Baseline weight Weight loss
mmol/L kg kg
HP diet
TG 1.5 mmol/L (n ҃ 27) 0.89 0.04 89.1 2.8 7.3 0.8
TG 1.5 mmol/L (n ҃ 25) 1.89 0.16 85.4 1.6 7.9 0.4
HC diet
TG 1.5 mmol/L (n ҃ 23) 0.90 0.04 86.5 2.6 8.1 0.7
TG 1.5 mmol/L (n ҃ 25) 1.99 0.13 86.2 2.5 5.8 0.7
2
1
All values are x SEM. HP, high protein; HC, high carbohydrate. There was no significant difference in baseline weight by diet or TG-status.
There was a significant interaction between diet and TG status (P ҃ 0.032) by repeated-measures ANOVA, with diet and TG status as between-subject
factors. The main effect of neither TG status (P ҃ 0.227) nor the main effect of diet (P ҃ 0.286) was significant.
2
Significant difference for change between diets (P ҃ 0.005) by univariate analysis, with baseline BMI as a covariate.
TABLE 5
Body-composition changes assessed by dual-energy X-ray
absorptiometry
1
HP group (n ҃ 52) HC group (n ҃ 48)
Total lean mass (kg)
2
Week 0 41.8 0.8 40.9 0.9
Week 12 40.3 0.9 39.3 1.0
Change Ҁ1.5 0.3 Ҁ1.8 0.3
Total fat mass (kg)
2
Week 0 42.1 1.2 41.9 1.1
Week 12 36.5 1.1 37.1 1.1
Change
3
Ҁ5.7 0.6 Ҁ4.5 0.5
Midriff lean fat (kg)
2
Week 0 2.4 0.1 2.5 0.1
Week 12 2.2 0.1 2.4 0.1
Change Ҁ0.2 0.1 Ҁ0.2 0.1
Midriff fat (kg)
2
Week 0 3.6 0.1 3.7 0.2
Week 12 2.7 0.1 3.0 0.1
Change
3
Ҁ0.9 0.1 Ҁ0.7 0.1
1
All values are x SEM. HP, high protein; HC, high carbohydrate.
There were no significant differences at baseline between diets.
2
Main effect of time (P 0.01) by repeated-measures ANOVA with
both time points as within-subject variables over both treatments.
3
There were no significant main effects of diet or triacylglycerol status,
but there was a significant diet ҂ triacylglycerol status interaction for total fat
(P ҃ 0.019) and midriff fat (P ҃ 0.03) by repeated-measures ANOVA with
diet and triacylglycerol status as between-subject factors. See Figure 2 for
subgroup analysis.
FIGURE 2. Mean (SEM) changes in total and midriff fat assessed by
dual-energy X-ray absorptiometry, by serum triacylglycerol (TG) status
(high or low concentrations), in subjects who consumed a high-protein (HP)
diet or a high-carbohydrate (HC) diet for 12 wk. There was no significant
difference at baseline in total or midriff fat mass by diet or TG status. There
were no significant main effects of diet or TG status, but there was a sig-
nificant diet ҂ TG status interaction for total fat (P ҃ 0.019) and midriff fat
(P ҃ 0.03) by repeated-measures ANOVA, with diet and TG status as
between-subject factors. Bars with different lowercase letters are signifi-
cantly different, P ҃ 0.035 (Tukey’s test for post hoc analysis). HP low TG
(n ҃ 27), HC low TG (n ҃ 23), HP high TG (n ҃ 25), HC high TG (n ҃ 25).
TABLE 6
Markers of renal function
1
Week 0 Week 12
Urine urea:creatinine
HP group (n ҃ 50) 33.7 1.29 38.2 0.88
2
HC group (n ҃ 48) 32.5 1.5 34.2 1.2
Serum urea (mmol/L)
HP group (n ҃ 50) 5.5 0.2 6.2 0.2
3
HC group (n ҃ 48) 5.8 0.2 5.1 0.2
Creatinine clearance (mL/min)
4
HP group (n ҃ 50) 82.3 3.3 76.7 2.9
HC group (n ҃ 48) 81.9 3.3 72.9 3.1
1
All values are x SEM. HP, high protein; HC, high carbohydrate.
There were no significant differences at baseline between diets.
2
Significantly different from HC group, P ҃ 0.003 (univariate analysis
at week 12 with week 0 as covariate).
3
Significantly different from HC group, P 0.001 (univariate analysis
at week 12 with week 0 as covariate).
4
No significant difference between diets, P ҃ 0.346 (univariate anal-
ysis at week 12 with week 0 as covariate).
1302 NOAKES ET AL
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significantly, by 28% compared with only 10% with the HC diet.
In the low- triacylglycerol group, there was no significant effect
of diet composition on triacylglycerol (Figure 3). Fasting glu-
cose, insulin, and free fatty acid concentrations all decreased
significantly with weight loss, with no differential effect of diet
composition (Table 7). CRP decreased significantly overall, by
19% (P 0.001), with no significant effect of diet (P ҃ 0.447).
The change in CRP in the low- triacylglycerol group was 0.74
0.27 mg/L, and the change in the high- triacylglycerol group was
1.90 0.41 mg/L (P ҃ 0.03 for the difference). This difference
was enhanced (P ҃ 0.018) after adjustment for weight loss.
Iron status
There was a small but nonsignificant 2% increase in hemo-
globin with the HP diet (P ҃ 0.116) but no change with the HC
diet (Table 8). Transferrin decreased by 9 –12% with both diets.
There were no significant changes in iron status. Ferritin con-
centrations were outside the normal range of 150
g/L in 17
subjects, which suggested that iron stores were likely to be re-
plete and nonresponsive to dietary changes. When these subjects
were excluded from the analysis, there was a significant 41%
increase in serum ferritin in the HP group but no change in this
marker of iron stores in the HC group (P ҃ 0.004 for diet effect;
Figure 4). It is interesting to note that ferritin, which has been
argued to be an additional marker for metabolic syndrome, was
positively correlated with serum homocysteine concentrations at
baseline (r ҃ 0.209, P ҃ 0.037).
Vitamins B-12 and B-6, homocysteine, and folate
Vitamin B-12 rose significantly (by 9%) with the HP diet,
whereas it decreased (by 13%) with the HC diet (Table 8). The
TABLE 7
Fasting lipid, glucose, insulin, free fatty acid, and C-reactive protein (CRP) concentrations
1
Week 0 Week 4 Week 8 Week 12 Change
P for
diet
2
P for
time
3
Triacylglycerol (mmol/L)
4
HP group 1.37 0.11
5
1.08 0.06 1.10 0.06 1.07 0.06 Ҁ0.30 0.10
HC group 1.47 0.11 1.31 0.09 1.3 0.09 1.35 0.10 Ҁ0.11 0.06 0.007 0.001
Total cholesterol (mmol/L)
HP group 5.75 0.16 4.97 0.14 5.14 0.14 5.26 0.15 Ҁ0.48 0.10
HC group 5.88 0.14 5.12 0.14 5.26 0.15 5.54 0.15 Ҁ0.33 0.08 0.164 0.001
LDL cholesterol (mmol/L)
HP group 3.79 0.14 3.32 0.13 3.43 0.13 3.53 0.13 Ҁ0.26 0.09
HC group 3.90 0.12 3.39 0.12 3.51 0.13 3.71 0.13 Ҁ0.19 0.08 0.399 0.001
HDL cholesterol (mmol/L)
HP group 1.33 0.05 1.17 0.04 1.21 0.04 1.25 0.04 Ҁ0.09 0.02
HC group 1.32 0.04 1.15 0.03 1.17 0.04 1.22 0.04 Ҁ0.09 0.02 0.657 0.001
Glucose (mmol/L)
HP group 6.16 0.65 6.00 0.59 6.13 0.66 5.93 0.61 Ҁ0.21 0.05
HC group 6.08 0.58 5.97 0.53 6.00 0.54 5.83 0.62 Ҁ0.25 0.07 0.589 0.001
Insulin (mU/L)
HP group 10.0 0.9 7.2 0.5 7.4 0.7 7.3 0.5 Ҁ2.7 0.5
HC group 10.0 0.7 7.5 0.5 7.9 0.8 8.4 1.2 Ҁ1.6 0.9 0.278 0.001
Free fatty acids (mmol/L)
HP group 0.46 0.03 0.45 0.03 0.39 0.02 0.42 0.03 Ҁ0.04 0.03
HC group 0.41 0.02 0.43 0.02 0.37 0.02 0.39 0.02 Ҁ0.02 0.02 0.765 0.001
CRP (mg/L)
HP group 6.6 0.7 4.9 0.6 Ҁ1.7 0.4
HC group 4.8 0.5 4.0 0.4 Ҁ0.8 0.3 0.447 0.001
1
HP, high protein (n ҃ 52); HC, high carbohydrate (n ҃ 48). There were no significant differences in variables at baseline between diets.
2
Main effect of diet by univariate analysis at week 12 with diet as the fixed factor and the week 0 data point as the covariate.
3
Main effect of time by repeated-measures ANOVA with all time points as within-subject variables over both treatments.
4
Significant diet ҂ triacylglycerol status interaction (P ҃ 0.023) by repeated-measures ANOVA with all time points and diet and triacylglycerol status
as between-subject factors. See Figure 3 for subgroup analysis.
5
x SEM (all such values).
FIGURE 3. Mean (SEM) changes in triacylglycerol (TG) concentra-
tions, by serum TG status (high or low concentrations), in subjects who
consumed a high-protein (HP) diet or a high-carbohydrate (HC) diet for 12
wk. There was a significant main effect of time (P 0.0001), a significant
main effect of diet (P ҃ 0.032), and a significant time ҂ diet ҂ TG status
interaction (P ҃ 0.023) by repeated-measures ANOVA with diet and TG
status as between-subject factors. Bars with different lowercase letters are
significantly different, P 0.05 (Tukey’s test for post hoc analysis). HP
low TG (n ҃ 27), HC low TG (n ҃ 23), HC high TG (n ҃ 25), HP high
TG (n ҃ 25).
EFFECT OF A LOW-FAT, HIGH-PROTEIN DIET 1303
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difference between diets was significant (P 0.0001). Vitamin
B-6 increased with both diets, with no significant difference
between them, whereas homocysteine did not change signifi-
cantly over the intervention. Serum folate increased marginally
with time (P ҃ 0.045), with no effect of diet composition (P ҃
0.234 for diet).
Markers of bone turnover
Osteocalcin increased by 23%, with no significant difference
between dietary interventions (Table 8). There was no correla-
tion between the amount of weight lost and changes in urinary
crosslinks or the calcium-creatinine ratio. The urinary crosslinks
and the calcium-creatinine ratio, however, were inversely related
(r ҃ 0.36 for pyridinoline and r ҃ 0.28 for deoxypyridinoline),
ie, the greater the decrease in calcium excretion, the smaller the
increase in crosslink excretion. Changes in crosslinks or osteo-
calcin were unrelated to menopausal or triacylglycerol status.
Osteocalcin at week 12 was correlated with the urinary
crosslinks at week 12 (P 0.01) after the adjustment for baseline
osteocalcin, but was not related to weight changes (P ҃ 0.723).
However, the urinary crosslinks at week 12 were both correlated
with the change in weight (P 0.01) and in osteocalcin (P
0.05) after the adjustment for baseline values. This suggests that
weight loss drives increased bone loss and there is partial com-
pensation with increased bone formation.
TABLE 8
Iron status, vitamin status, and markers of bone turnover
1
Week 0 Week 12 Change P for diet
2
P for time
3
Hemoglobin (g/L)
HP group 132 1
4,5
135 13 1—
HC group 138 1 138 10 1 0.116 0.066
Transferrin (
mol/L)
HP group 34.3 0.9 30.3 0.8 Ҁ4.1 0.4
HC group 34.0 0.9 30.8 0.9 Ҁ3.1 0.5 0.148 0.001
Transferrin saturation (%)
HP group 23.9 1.3 24.6 1.3 0.6 1.2
HC group 27.0 1.3 27.9 1.2 0.4 1.4 0.383 0.554
Ferritin (
g/L)
HP group 105 23 120 17 15 10
HC group 83 990 12 7 6 0.144 0.064
Iron (
mol/L)
HP group 16.0 0.7
6
14.6 0.6 Ҁ1.1 0.6
HC group 18.0 0.9 16.2 0.6 Ҁ1.8 0.9 0.267 0.010
Serum vitamin B-12 (pmol/L)
HP group 273 14 311 21 38 13
HC group 278 14 240 13 Ҁ38 7 0.0001 0.865
Pyridoxyl phosphate activation (%)
HP group 50.3 1.4 47.0 1.0 Ҁ3.1 1.2
HC group 47.3 1.7 44.9 1.5 Ҁ2.4 1.0 0.602 0.001
Serum homocysteine (
mol/L)
HP group 8.5 0.2 8.5 0.2 0.1 0.2
HC group 8.8 0.3 8.7 0.2 0.1 0.2 0.733 0.596
Serum folate (nmol/L)
HP group 26.3 1.0 26.7 0.7 0.4 0.9
HC group 24.8 1.1 27.1 0.7 2.3 0.9 0.265 0.045
Serum osteocalcin (ng/mL)
HP group 6.75 0.56 7.95 0.46 1.20 0.3
HC group 5.49 0.49 7.03 0.48 1.54 0.3 0.997 0.0001
Deoxypyridinoline:creatinine (nmol/mmol)
HP group 22.2 1.4 24.7 1.0 2.5 1.1
HC group 20.5 0.9 24.2 1.3 3.7 1.0 0.786 0.0001
Pyridinolone:creatinine (nmol/mmol)
HP group 78.7 5.3 84.3 2.8 5.6 4.0
HC group 69.3 2.4 77.6 3.1 8.2 2.1 0.493 0.003
1
HP, high protein (n ҃ 52); HC, high carbohydrate (n ҃ 48).
2
Main effect of diet by univariate analysis at week 12 with diet as the fixed factor and the week 0 data point as the covariate.
3
Main effect of time by repeated-measures ANOVA with both time points as within-subject variables over both treatments.
4
x SEM (all such values).
5,6
Significantly different from HC group:
5
P ҃ 0.004,
6
P ҃ 0.045.
FIGURE 4. Mean (SEM) plasma ferritin concentrations, adjusted to
exclude subjects with baseline ferritin concentrations exceeding the normal
range (150
g/L), in subjects who consumed a high-protein (HP; n ҃ 43)
diet or a high-carbohydrate (HC; n ҃ 40) diet for 12 wk.
*
Significantly
different from the HP diet at week 12, P ҃ 0.002 (univariate analysis with diet
as the fixed factor and the week 0 data point as the covariate).
1304 NOAKES ET AL
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DISCUSSION
Although we hypothesized that the HP diet would result in
greater fat loss and less lean mass loss than the HC diet, we did
not observe this for the group of overweight women overall. This
finding contrasts with that of our previous studies in subjects with
type 2 diabetes (8) and hyperinsulinemia (9), hence, our sub-
group analysis to ascertain whether markers of the insulin resis-
tance syndrome may have predicted responses to the dietary
interventions. In our study, overweight women with high triacyl
glycerol concentrations, one of the key markers of the insulin
resistance syndrome, lost 50% more total fat with the HP diet
than with the HC diet. Although further confirmation is required,
we believe that this is the first study to suggest a phenotype ҂ diet
interaction with respect to the magnitude of weight loss to dif-
ferent diet interventions. Although we speculate that the HP diet
provided increased satiety and, hence, subsequent lower energy
intake, there was no suggestion of this from reported dietary
intakes or differences in physical activity between groups. In a
study by Johnston et al (15), subjects who consumed an energy-
restricted dietary pattern providing 30% of energy from protein
reported less hunger than did those who consumed a high-
carbohydrate dietary pattern. However, we cannot rule out the
likelihood that the food records may not be suitably accurate to
detect a difference of 100 kJ/d between groups, which is the extra
energy deficit needed to result in a 1.9-kg weight difference over
12 wk. The mechanism for why this was observed only in the
group with elevated triacylglycerol concentrations is of interest.
McLaughlin et al (16) showed that the use a cutoff of 1.47
mmol/L is useful in identifying overweight persons who are
insulin resistant. However, they showed no differences in weight
loss with a hypocaloric diet, on the basis of the degree of insulin
resistance (17). A high triacylglycerol concentration may be a
marker for the
2
-adrenoceptor Gln27Glu polymorphism (18).
-Adrenergic receptors play an important role in the regulation
of energy expenditure and lipid mobilization. A Gln27Glu poly-
morphism in the
2
-adrenergic receptor gene has been shown to
be associated with several indexes of obesity in a female, white
population, and obesity was shown to be significantly more prev-
alent in high-carbohydrate consumers with this polymorphism
(19). In addition, both lipolysis and fat oxidation appear to be
blunted in obese polymorphic Glu27Glu subjects (20), which
suggests a rationale for the enhanced fat loss in our subgroup with
high triacylglycerol concentrations who consumed the lower-
carbohydrate HP diet.
Concerns that diets high in meat protein may have deleterious
effects on renal function and bone turnover were not substanti-
ated by this study, which showed similar reductions in creatinine
clearance with both dietary patterns as a consequence of body
mass change. Skov et al (21) assessed changes in renal function
by measuring the glomerular filtration rate during high-protein
and high-carbohydrate diets over a 6-mo period and also con-
cluded that the HP diet had no adverse effects on kidney function.
Johnston et al (15) observed that creatinine clearance was not
altered by dietary protein in the context of weight loss, and
nitrogen balance was more positive in subjects who consumed
the HP diet than in those who consumed the HC diet. Whether this
is also true in subjects with compromised kidney function has not
been studied, although we have shown an improvement in mi-
croalbuminuria in subjects with type 2 diabetes after weight loss
with either a high-protein or a high-carbohydrate diet, which
suggests that weight loss and consequent blood pressure reduc-
tion may be more important in ameliorating renal function than
is dietary protein. Last, although the amount of dietary protein
was proportionally high, it was not high in absolute terms. The
HP diet provided 104 g and the HC diet provided 58 g protein,
which is within the range of protein intakes in the Australian
population (22). In fact, these intakes represent the 95th percen-
tile and the 20th percentile of protein intakes for women of this
age group in Australia.
The effect of this level of protein on markers of bone turnover
was similarly not deleterious. Although weight loss appears to
enhance both bone breakdown and, secondarily, bone formation,
these variables were not significantly different between the 2 diet
groups. Other studies have shown that diet-induced weight loss
in postmenopausal women is associated with general bone loss,
probably because of reduced mechanical strain on the skeleton
(23), but that premenopausal women do not lose bone even if they
have a low calcium intake during weight loss (24). Evidence also
indicates that higher protein intakes, particularly higher animal
protein intakes, are associated with decreased bone loss in older
persons (25). The reduction in urinary calcium in this study was
also unusual because dietary protein metabolism is associated
with increased urinary calcium (26). The high vegetable con-
sumption with both dietary patterns may have prevented this
because high vegetable intakes have been shown to decrease
urinary calcium (27). An increase in calcium excretion was ob-
served with the consumption of a high-protein diet in the study by
Johnston et al (15), who state that this was due to the high calcium
content of the high-protein diet in this study. However, we did not
observe this in other studies of high-protein patterns in which
dietary calcium was very high, ie, 2400 mg/d (28).
Cardiovascular disease markers improved with weight loss
with both diets; triacylglycerol concentrations decreased more
with the HP diet in women with elevated triacylglycerol concen-
trations. This finding reflects a lower carbohydrate load with the
HP diet, which results in reduced VLDL TG production (29).
CRP, which is known to decrease with weight loss (30), was not
influenced by dietary composition, although there was a sugges-
tion that the HP diet lowered CRP more effectively in women
with higher triacylglycerol concentrations. This observation
warrants further investigation.
Dietary patterns intended for weight loss, which sustain or
improve nutritional status, are important for optimum health. The
HC diet pattern was designed to provide a contrasting intake of
protein and, as such, did not fully meet the recommended dietary
allowance (RDA) for some nutrients, notably calcium and iron.
In contrast, nutrient intakes with the HP diet were adequate or
exceeded the RDA, which reflected the higher proportion of
nutrient-dense protein foods from dairy foods and lean meat in
the diet. Hemoglobin concentrations were maintained with both
diets. This is in contrast with the findings of Kretsch et al (31),
who fed dieting obese women dietary iron at twice the US
RDA— half of which was from food and half of which was from
an oral supplement—yet found a significant reduction in hemo-
globin concentrations. This group also found that hemoglobin
and transferrin saturation were both positively correlated with
mean performance on a measure of sustained attention. The sta-
bility of iron status in the HC group was surprising given both the
quantitatively lower iron intake and the theoretically lower bio-
availability of iron with this diet, but the higher fruit and vege-
table intake may have contributed to optimizing iron absorption.
EFFECT OF A LOW-FAT, HIGH-PROTEIN DIET 1305
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Pyridoxal phosphate activation, a marker of vitamin B-6 sta-
tus, decreased with weight loss with both diets, which indicated
improved vitamin B-6 status. Vitamin B-6 functions as a cofactor
in enzymes involved in transamination reactions required for the
synthesis and catabolism of the amino acids as well as in glyco-
genolysis as a cofactor for glycogen phosphorylase. Vitamin B-6
is found in a wide variety of foods, including beans, meat, poul-
try, fish, and some fruit and vegetables. Improved vitamin B-6
status is likely to be a function of the improved nutrient density
of both dietary patterns compared with baseline eating patterns.
The greatest difference in nutrient status was observed with
serum vitamin B-12, which increased by 9% with the HP diet but
decreased by 13% with the HC diet. This finding reflected the
difference in animal protein sources between the 2 dietary pat-
terns. Ames (32) postulated that micronutrient deficiencies are a
major cause of DNA damage by the same mechanism as radiation
and many chemicals. Intervention studies in humans have shown
that DNA damage is minimized when, among other micro-
nutrients such as folate, serum concentration of vitamin B-12
are 300 pmol/L, which is precisely the concentration achieved
with the HP diet in this study without supplementation.
In conclusion, both the HP and HC, which were intended for
weight loss, resulted in significant improvements in markers of
cardiovascular disease risk, although the HP diet resulted in a
greater reduction in triacylglycerol concentrations and improve-
ments in hemoglobin and vitamin B-12 status. An energy-
restricted diet high in protein from lean red meat and low-fat
dairy products seems to provide a weight loss advantage in sub-
jects with elevated triacylglycerol concentrations—a marker of
the metabolic syndrome. This finding requires confirmation in
future studies in hypertriglyceridemic women. There was no
evidence of adverse effects on bone or renal metabolism with
either diet over the 12-wk study period.
We thank Anne McGuffin, Kathryn Bastiaans, and Rosemary McArthur
for assistance with the performance of this study.
MN and PMC designed the study, performed the statistical analysis,andwrote
the manuscript. PRF and JBK contributed both to the interpretation of the dietary
data and to the preparation of the manuscript and were involved in the dietetic
counseling and data analysis. None of the authors had a conflict of interest.
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... Participants in both groups met with the dietitian monthly throughout the study. Based on previous studies, women and men were counseled to restrict energy intake to 5500 and 7000 kJ, respectively [21,22]. Participants in both groups were asked to keep their exercise patterns constant throughout the study. ...
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Diets for healthy aging have long been an intriguing issue. The current study makes a head-to-head comparison of four dietary patterns and their associations with soluble Klotho (s-Klotho) levels, an aging-related marker. The dietary data of 7906 subjects were obtained from the National Health and Nutrition Examination Survey 2007–2016. Each participant was given a score or was grouped according to four dietary patterns, namely the Mediterranean adherence diet score (MDS), the low-carbohydrate-diet score, a low-fat diet, and a low-carbohydrate diet. Subsequently, the associations with s-Klotho were examined using linear regression analyses. In addition, we calculated the odds ratio (OR) for aging in different dietary patterns, taking the lowest quartile of s-Klotho as a reference for aging. The MDS was the only dietary pattern that revealed a relationship with s-Klotho levels. The positive association (β coefficient: 9.41, p < 0.001) remained significant when dividing the MDS into tertiles (Tertile 2: β coefficient: 36.87, p < 0.001; Tertile 3: β coefficient: 45.92, p < 0.001) and grouping participants into subsets by sex, age, and BMI. A lower OR for aging was observed in higher MDS groups (Tertile 2: OR = 0.86, p = 0.026; Tertile 3: OR = 0.77, p < 0.001). However, when analyzed separately, merely three out of nine components of the MDS, namely alcohol consumption (β coefficient: 42.54, p < 0.001), fruit (β coefficient: 11.59, p = 0.029), and dairy products (β coefficient: 8.55, p = 0.032), showed a significant association with s-Klotho. The Mediterranean diet adopts a food-based approach, which has the merit of valuing the complex interactions between foods and their constituents, and further brings benefits to healthy aging.
... As a result, HP diets do not impair bone health but potentially offer a mechanical (maintained fat-free mass), biochemical (increased IGF-1), and homeostatic (increased calcium absorption) advantage in preserving bone mass during ER. Yet, even with a recent meta-analysis showing a positive effect of HP diets on BMD during ER [37], confusion persists in the scientific community with studies that show an attenuation [35,36,38], exacerbation [39], or neutral effect [40,41] of HP-ER diets on WL-induced bone loss. ...
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Higher protein (>30% of total energy, HP)-energy restriction (HP-ER) diets are an effective means to improve body composition and metabolic health. However, weight loss (WL) is associated with bone loss, and the impact of HP-ER diets on bone is mixed and controversial. Recent evidence suggests conflicting outcomes may stem from differences in age, hormonal status, and the predominant source of dietary protein consumed. Therefore, this study investigated the effect of four 12-week energy restriction (ER) diets varying in predominate protein source (beef, milk, soy, casein) and protein quantity (normal protein, NP 15% vs. high, 35%) on bone and body composition outcomes in 32-week-old obese, ovariectomized female rats. Overall, ER decreased body weight, bone quantity (aBMD, aBMC), bone microarchitecture, and body composition parameters. WL was greater with the NP vs. HP-beef and HP-soy diets, and muscle area decreased only with the NP diet. The HP-beef diet exacerbated WL-induced bone loss (increased trabecular separation and endocortical bone formation rates, lower bone retention and trabecular BMC, and more rod-like trabeculae) compared to the HP-soy diet. The HP-milk diet did not augment WL-induced bone loss. Results suggest that specific protein source recommendations may be needed to attenuate the adverse alterations in bone quality following an HP-ER diet in a model of postmenopausal obesity.
... Some randomised trials comparing higher protein diets to lower protein diets have reported decreases in body weight (11,(37)(38)(39)(40) and greater fat loss with higher protein diets (11,38,41) . However, other trials have found that higher protein diets did not result in increased weight loss compared with other diets, especially over the long term (41)(42)(43) .A meta-analysis of thirty-two trials with greater than 12 months of follow up found that although higher protein diets showed benefits for weight loss in the short term, these benefits persisted to a smaller degree in the long term. However, greater benefits were observed long term in those with better compliance to higher-protein diets (44) . ...
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Objective This study investigated associations between types and food sources of protein with overweight/obesity and underweight in Ethiopia. Design We conducted a cross-sectional dietary survey using a non-quantitative food frequency questionnaire. Linear regression models were used to assess associations between percent energy intake from total, animal, and plant protein and body mass index (BMI). Logistic regression models were used to examine associations of percent energy intake from total, animal, and plant protein and specific protein food sources with underweight and overweight/obesity. Setting Addis Ababa, Ethiopia. Participants 1,624 Ethiopian adults (992 women and 632 men) aged 18-49 years in selected households sampled using multi-stage random sampling from five sub-cities of Addis Ababa, Ethiopia. Results Of the surveyed adults, 31% were overweight or obese. The majority of energy intake was from carbohydrate with only 3% from animal protein. In multivariable-adjusted linear models, BMI was not associated with percent energy from total, plant or animal protein. Total and animal protein intake were both associated with lower odds of overweight/obesity (Odds Ratio [OR] per 1% energy increment of total protein 0.92; 95% CI: 0.86, 0.99; P=0.02; OR per 1% energy increment of animal protein 0.89; 95% CI: 0.82, 0.96; P=0.004) when substituted for carbohydrate and adjusted for sociodemographic covariates. Conclusions Increasing proportion of energy intake from total protein or animal protein in place of carbohydrate could be a strategy to address overweight and obesity in Addis Ababa; longitudinal studies are needed to further examine this potential association.
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Food intake and body weight regulation are of special interest for meeting today’s lifestyle essential requirements. Since balanced energy intake and expenditure are crucial for healthy living, high levels of energy intake are associated with obesity. Hence, regulation of energy intake occurs through shortand longterm signals as complex central and peripheral physiological signals control food intake. This work aims to explore and compile the main factors influencing satiating eciency of foods by updating recent knowledge to point out new perspectives on the potential drivers of satiety interfering with food intake regulation. Human internal factors such as genetics, gender, age, nutritional status, gastrointestinal satiety signals, gut enzymes, gastric emptying rate, gut microbiota, individual behavioral response to foods, sleep andcircadian rhythmsarelikely tobeimportantindeterminingsatiety. Besides, theexternal factors (environmentalandbehavioral)impactingsatietyeciency are highlighted. Based on mechanisms related to food consumption and dietary patternsseveralphysical,physiological,andpsychologicalfactorsaect satiety or satiation. A complex network of endocrine and neuroendocrine mechanisms controls the satiety pathways. In response to food intake and other behavioral cues, gut signals enable endocrine systems to target the brain. Intestinal and gastric signals interact with neural pathways in the central nervous system to halt eating or induce satiety. Moreover, complex food composition and structures result in considerable variation in satiety responses for dierent food groups. A better understanding of foods and factors impacting the eciency of satiety could be helpful in making smart food choices and dietary recommendations for a healthy lifestyle based on updated scientific evidence.
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Background: Cryolipolysis is characterized by localized and controlled cooling of the subcutaneous adipose tissue, in a non-invasive way, causing a localized panniculitis, followed by adipocyte death by apoptosis and, consequently, a decrease in adipose tissue in the treated area. Aim(s): To evaluate the scientific evidence and methodological qualities about effects, adverse reactions, and level of satisfaction of cryolipolysis for the reduction of subcutaneous adipose tissue. Methods: A systematic review was carried out according to the PRISMA recommendation. Searches were conducted in different databases. We included studies that used a randomized control and self-control design and were carried out in humans. Articles published in English and Portuguese were screened, with no time limit regarding the year of publication. The methodological quality of the studies was assessed using the Cochrane Rob2 scale. Results: Of 381 articles, seven were considered eligible for inclusion. After applying the Cochrane Rob2 scale, five studies were included in the final sample. Most studies showed significant results for cryolipolysis in reducing localized fat. The incorporation of a dietary program into the treatment was shown to contribute to a significant improvement in the lipid profile and liver enzymes, which does not happen when cryolipolysis is applied in isolation. Rare adverse effects have been identified, but never persisting beyond a month. Conclusions: Cryolipolysis is an effective technique for reducing localized fat, safe, and well tolerated, with most participants satisfied at the end of the treatment. However, more randomized controlled studies should be carried out, since there is a limited number of articles with good methodological quality.
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Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver disorders with a relatively high mortality rate. Berberine has recently been found to have some antidiabetic and antihyperlipidemic effects, although the evidence of its effectiveness in NAFLD is limited. To assess the efficacy of berberine among patients with NAFLD. Methods: The patients with NAFLD were randomly assigned to treatment with (n = 25) or without (n = 25) berberine. The patients in the intervention group took berberine 6.25 g per day and the control group had no berberine. All patients in the 2 groups had been recommended to have lifestyle training, including a low-fat diet and physical activity before randomization. Independent student t tests or Mann-Whitney U tests along paired t tests or Wilcoxon signed-rank tests were used. Analysis of covariance was also used to estimate the difference of the variables between the 2 groups adjusting for baseline characteristics. Results: The results indicated that berberine, compared with the control group, had no significant impact on lipid levels, including triglyceride (P = 0.350), total cholesterol (P = 0.120), high-density lipoproteins (P = 0.401), and low-density lipoproteins (P = 0.100). Similarly, no significant difference was observed between the treatment arms in the level of fasting blood glucose (P = 0.055) and liver enzymes, such as alkaline phosphatase (P = 0.109), serum glutamic-oxaloacetic transaminase (P = 0.366), and serum glutamic pyruvic transaminase (P = 0.436). The effect of berberine on body weight was also nonsignificant (P = 0.494) and even smaller than that of liver enzymes, with a mean difference of 1.8 kg (P = 0.304) in body weight. Conclusion: Berberine was not associated with a significant decrease in lipid profile, fasting blood glucose, or liver enzymes among patients with NAFLD.
Chapter
This chapter describes many of the different dietary protocols currently used and the evidence behind them. In addition to documenting the actual diet consumed, a food diary may also reveal an erratic eating pattern, irregular meals, periods of fasting, excessively restricted eating, frequent snacking, grazing, or binge eating. Evidence shows that augmenting the diet with low‐density food enhances weight loss but only when the food is palatable enough to ensure compliance. Low‐fat diets are as good as other interventions at reducing weight but not better. Plant‐based eating is common in traditional societies, particularly in the Mediterranean and in Asia. Advantages of partial meal replacement therapy over full meal replacements are that they offer participants choice and flexibility in social situations whilst reducing decision making at other times. The fundamental aim of dietary management in overweight and obesity is to create an energy deficit that achieves weight loss and that can be maintained long term.
Conference Paper
Objective: The recent literature suggests that high-protein, low-fat diets promote a greater degree of weight loss compared to high-carbohydrate, low-fat diets, but the mechanism of this enhanced weight loss is unclear. This study compared the acute, energy-cost of meal-induced thermogenesis on a high-protein, low-fat diet versus a high-carbohydrate, low-fat diet. Methods: Ten healthy, normal weight, non-smoking female volunteers aged 19-22 years were recruited from a campus population. Using a randomized, cross-over design, subjects consumed the high-protein and the high-carbohydrate diets for one day each, and testing was separated by a 28- or 56-day interval. Control diets were consumed for two days prior to each test day. On test day, the resting energy expenditure, the non-protein respiratory quotient and body temperature were measured following a 10-hour fast and at 2.5-hour post breakfast, lunch and dinner. Fasting blood samples were collected test day and the next morning, and complete 24-hour urine samples were collected the day of testing. Results: Postprandial thermogenesis at 2.5 hours post-meal averaged about twofold higher on the high protein diet versus the high carbohydrate diet, and differences were significant after the breakfast and the dinner meals (p < 0.05). Body temperature was slightly higher on the high protein diet (p = 0.08 after the dinner meal). Changes in the respiratory quotient post-meals did not differ by diet, and there was no difference in 24-hour glomerular filtration rates by diet. Nitrogen balance was significantly greater on the high-protein diet compared to the high-carbohydrate diet (7.6 +/- 0.9 and -0.4 +/- 0.5 gN/day, p < 0.05), and at 24-hour post-intervention, fasting plasma urea nitrogen concentrations were raised on the high protein diet versus the high-carbohydrate diet (13.9 +/- 0.9 and 11.2 +/- 1.0 mgJdL respectively, p < 0.05). Conclusions: These data indicate an added energy-cost associated with high-protein, low-fat diets and may help explain the efficacy of such diets for weight loss.
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Background: Insulin resistance is more common in overweight individuals and is associated with increased risk for type 2 diabetes mellitus and cardiovascular disease. Given the current epidemic of obesity and the fact that lifestyle interventions, such as weight loss and exercise, decrease insulin resistance, a relatively simple means to identify overweight individuals who are insulin resistant would be clinically useful. Objective: To evaluate the ability of metabolic markers associated with insulin resistance and increased risk for cardiovascular disease to identify the subset of overweight individuals who are insulin resistant. Design: Cross-sectional study. Setting: General clinical research center. Patients: 258 nondiabetic, normotensive overweight volunteers. Measurements: Body mass index; fasting glucose, insulin, lipid and lipoprotein concentrations; and insulin-mediated glucose disposal as quantified by the steady-state plasma glucose concentration during the insulin suppression test Overweight was defined as body mass index of 25 kg/m 2 or greater, and insulin resistance was defined as being in the top tertile of steady-state plasma glucose concentrations. Receiver-operating characteristic curve analysis was used to identify the best markers of insulin resistance; optimal cut-points were identified and analyzed for predictive power. Results: Plasma triglyceride concentration, ratio of triglyceride to high-density lipoprotein cholesterol concentrations, and insulin concentration were the most useful metabolic markers in identifying insulin-resistant individuals. The optimal cut-points were 1.47 mmol/L (130 mg/dL) for triglyceride, 1.8 in SI units (3.0 in traditional units) for the triglyceride-high-density lipoprotein cholesterol ratio, and 109 pmol/L for insulin. Respective sensitivity and specifity for these cut-points were 67%, 64%, and 57% and 71%, 68%, and 85%. Their ability to identify insulin-resistant individuals was similar to the ability of the criteria proposed by the Adult Treatment Panel III to diagnose the metabolic syndrome (sensitivity, 52%, and specificity, 85%). Conclusions: Three relatively simple metabolic markers can help identify overweight individuals who are sufficiently insulin resistant to be at increased risk for various adverse outcomes. In the absence of a standardized insulin assay, we suggest that the most practical approach to identify overweight individuals who are insulin resistant is to use the cut-points for either triglyceride concentration or the triglyceride-high-density lipoprotein cholesterol concentration ratio.
Article
This study tests the hypothesis that hyperinsulinemic (HI) obese subjects respond differently from normoinsulinemics (NI) to changes in composition of hypoenergetic diets. Twenty-seven obese male subjects, 13 HI and 14 NI, were fed for 4 weeks either a high protein (HP) or a high carbohydrate (HC) hypoenergetic diet providing 80% of their resting energy expenditure (REE). On the HP diet weight loss was significantly higher in HI as compared to NI group. Alternatively, the HI group lost less weight than NI group on the HC diet. The HC diets resulted in a considerable and similar reduction in REE in both HI and NI groups as opposed to the HP diet, which maintained REE in both HI and NI. A higher decrease and normalization of fasting insulin levels was observed in the HI group on the HP as compared to HC diet. In conclusion, hyperinsulinemic, in contrast to normoinsulinemic obese subjects, seem to achieve better weight reduction, less decline in energy expenditure, and normalization of insulin levels on HP than isocaloric HC diet.
Article
Bone turnover is increased during weight loss in postmenopausal women and can be suppressed with calcium supplementation. In this study, we assessed the influence of energy restriction with and without calcium supplementation (1 g/day) in premenopausal women. Thirty-eight obese premenopausal women (body mass index [BMI] of 35.0 ± 3.9 kg/m2) completed a 6-month study of either moderate weight loss or weight maintenance. During weight loss, women were randomly assigned to either a calcium supplementation (n = 14) or placebo group (n = 14) and lost 7.5 ± 2.5% of their body weight. The control group of women (n = 10) maintained their body weight. Total body and lumbar bone mineral density (LBMD) and content were measured by dual-energy X-ray absorptiometry (DXA) at baseline and after weight loss. Throughout the study, blood and urine samples were collected to measure bone turnover markers and hormones. During moderate energy restriction, dietary calcium intake decreased (p < 0.05) and the bone resorption marker deoxypyridinoline (DPD) increased slightly (p ≤ 0.05) without evidence of bone loss. Calcium supplementation during weight loss tended to increase lumbar BMD by 1.7% (p = 0.05) compared with the placebo or weight maintenance groups. In contrast to our previous findings in postmenopausal women, premenopausal obese women who consume a low calcium diet do not lose bone over a 6-month period, whether their weight is stable or decreasing moderately.
Article
Few studies have evaluated protein intake and bone loss in elders. Excess protein may be associated with negative calcium balance, whereas low protein intake has been associated with fracture. We examined the relation between baseline dietary protein and subsequent 4-year change in bone mineral density (BMD) for 391 women and 224 men from the population-based Framingham Osteoporosis Study. BMD (g/cm2) was assessed in 1988-1989 and in 1992-1993 at the femur, spine, and radius. Usual dietary protein intake was determined using a semiquantitative food frequency questionnaire (FFQ) and expressed as percent of energy from protein intake. BMD loss over 4 years was regressed on percent protein intake, simultaneously adjusting for other baseline factors: age, weight, height, weight change, total energy intake, smoking, alcohol intake, caffeine, physical activity, calcium intake, and, for women, current estrogen use. Effects of animal protein on bone loss also were examined. Mean age at baseline (±SD) of 615 participants was 75 years (±4.4; range, 68-91 years). Mean protein intake was 68 g/day (±24.0; range, 14-175 g/day), and mean percent of energy from protein was 16% (±3.4; range, 7-30%). Proportional protein intakes were similar for men and women. Lower protein intake was significantly related to bone loss at femoral and spine sites (p ≤ 0.04) with effects similar to 10 lb of weight. Persons in the lowest quartile of protein intake showed the greatest bone loss. Similar to the overall protein effect, lower percent animal protein also was significantly related to bone loss at femoral and spine BMD sites (all p < 0.01) but not the radial shaft (p = 0.23). Even after controlling for known confounders including weight loss, women and men with relatively lower protein intake had increased bone loss, suggesting that protein intake is important in maintaining bone or minimizing bone loss in elderly persons. Further, higher intake of animal protein does not appear to affect the skeleton adversely in this elderly population.
Article
To assess the role of polymorphisms in the β2-adrenergic receptor gene in the development of obesity and obesity-related metabolic disorders, we analysed Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms in 400 non-obese subjects (body mass index < 27 kg/m2) and 108 obese subjects (body mass index ≥ 27 kg/m2). The Gln27Glu substitution was twice as common in obese subjects as in non-obese subjects (0.14 vs 0.07, p = 0.001, odds ratio 2.14, 95 % confidence interval 1.35–3.41). The frequency of the Glu27 allele was also higher in patients with Type II (non-insulin-dependent) diabetes mellitus than non-diabetic subjects (0.14 vs 0.07, p = 0.001, odds ratio 2.13, 95 % confidence interval 1.34–3.41). Analysis of variance of multiple variables showed an association between 2-h post-load glucose concentrations and body mass index but not with the Glu27 variant, suggesting that the association with diabetes could be secondary to obesity. Obese subjects carrying the variant allele had higher concentrations of serum triglyceride than obese subjects homozygous for the wild type allele (2.68 ± 1.90 vs 1.18 ± 1.15 mmol/l, p = 0.02). Conversely, the frequency of Gly16 homozygotes was lower in obese women when compared with non-obese women (11 % vs 28 %, p = 0.01, odds ratio 0.30, 95 % confidence interval 0.12–0.75), although the association was not present in male subjects. Thr164Ile substitution was not detected in the subjects of this study. These observations suggest that the amino-terminal polymorphisms of the β2-adrenergic receptor gene could be involved in the molecular pathogenesis of obesity and hypertriglyceridaemia, and thereby the development of Type II diabetes mellitus. [Diabetologia (1999) 42: 98–101]