2. Materials and Methods
2.1. Search Strategy
2.2. Eligiblity Criteria
2.3. Data Extraction
2.4. Statistical Analysis
3.1. Characteristics of Included Studies and Search Results
3.2. Effect of the Paleolithic Diet on Body Composition—Anthropometric Parameters (Body Mass, Body Mass Index, Waist Circumference, Fat Mass, and Fat Free Mass) in the Short (up to 6 Months) and Long (over 6 Months) Term
3.3. Effect of the Paleolithic Diet on Lipid Profile (Total Cholesterol, Triglycerydes, HDL-C, and LDL-C in the Short (up to 6 Months) and Long (over 6 Months) Term
3.4. Effect of the Paleolithic Diet on Blood Pressure (Systolic Blood Pressure, Diastolic Blood Pressure, and Heart Rate) in the Short (up to 6 Months) and Long (over 6 Months) Term
3.5. Effect of the Paleolithic Diet on Carbohydrates Metabolism (Fasting Plasma Glucose, Fasting Plasma Insulin, HOMA-IR, and HbA1c) in the Short (up to 6 Months) and Long (over 6 Months) Term
3.6. Effect of the Paleolithic Diet on Physical Capacity (Maximum Oxygen Uptake and Maximum Workload)
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
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|Study and Year||Type of Diets/|
Type of Study
|Subjects (n)/Participants Characteristic/Age/|
Duration of Intervention (Time)
|Effect on Body Composition||Effect on|
|Effect on Athletic Performance|
|Andersson et al. 2016 ||PD vs. CD (NNR)|
| healthy postmenopausal women with body mass index (BMI) ≥ 27 kg/m2 (overweigh/obese)|
long-term (24 months)
Both diet groups decreased their BM and BMI at 6 and 24 months without significant differences between groups.
|No effect: No difference in cholesterol levels over time or between groups.||Partially positive:|
BP was reduced at 6 months but returned to baseline levels at 24 months.
|No effect: No differences were observed over time or between groups regarding fasting glucose, insulin concentrations and HOMA-IR.||Not analyzed|
|Boers et al. 2014 ||PD vs. CD (Dutch Health Cuncil)|
| men (n = 9) and women (n = 25) with at least two characteristics of the metabolic syndrome|
PD: 52 ± 10.2
CD: 55 ± 9
short-term (2 week)
|Partially positive: In both groups, change was observed in WC.||Positive: Lower TC and TG and a higher mean HDL. The TC/HDL and TG/HDL ratios were lower in the PD compared to reference.||Positive: Lower SBP, DBP.||Positive:|
decreased fasting plasma insulin and HOMA-IR.
et al. 2017 
|PD vs. CD|
| postmenopausal women with over- weight|
PD: 60 ± 5.6
CD: 61 ± 7
short-term (6 months); long-term (24 months)
|Partially positive: Android fat decreased significantly more in the PD group during the first 6 months with weight maintenance at 24 months in both groups.||Positive: HDL levels increased in both groups between 6 and 24 months, LDL and TG levels decreased significantly in the PD group after 24 months.||Partially positive:|
In both groups, blood pressure decreased at 6 months, and the effect on DBP remained after 24 months in the PD group.
|Partially positive: HOMA-IR decreased significantly in 6 months for PD group, rest of effect statistically insignificant.||Not analyzed|
|Blomquist et al. 2018 ||PD vs. CD|
| postmenopausal women with over-weight/healthy|
PD: 60 ± 5.5
CD: 62 ± 5.7
short-term (6 months)
|Positive: significantly larger reductions in body weight and SAG in PD compared to the CD group.||Partially positive:|
TG decreased significantly more in the PD group compared to the CD group. TC levels and LDL decreased in both groups, without differences between groups. The levels of HDL and FFA remained stable in both groups.
The PD led to improved insulin sensitivity.
The HOMA-IR index decreased significantly in the PD group, without significant difference between diet groups.
|Boraxbekk et al. 2015 ||PD vs. CD (NNR)|
| overweight or obese postmenopausal women|
PD = 61 ± 1.6
CD = 61.6 ± 1.7
short-term (6 months)
PD and NNR improved anthropometric measurements without significant differences between groups.
Levels of FFA in plasma decreased in both groups.
|Not analyzed||No effects: no changes in plasma glucose, insulin, or HOMA-IR.||Not analyzed|
|Fontes- Villalba et al. 2016 ||PD vs. CD (diabetes diet)|
| patients with type 2 diabetes/|
PD: 66 ± 6
CD: 63 ± 6
short-term (12 weeks)
weight loss was significantly greater after the PD than the diabetes diet
|Not analyzed||Not analyzed||No effects: did not change fasting levels of insulin.||Not analyzed|
|Frassetto et al. 2009 ||3 days, three ramp-up diets of increasing potassium and fiber for 7 days, then a PD for 10 days;|
| nonobese sedentary healthy volunteers/healthy population in physical activity|
38 ± 12
short-term (10 day)
|Positive: large significant reductions in TC, LDL, and TG. No significant change occurred in HDL.||Positive: significant reductions in BP associated with improved arterial distensibility.||Positive: significant reduction in plasma insulin vs. time AUC during the OGTT.||Not analyzed|
|Genoni et al. 2016 ||PD vs. CD|
| healthy women with BMI 27 ± 4 kg/m2|
47 ± 13
short-term (4 weeks)
Significantly greater BM loss and WC occurred in the PD.
In both dietary groups experienced within group reductions to TC and LDL. No significant differences in these changes between the dietary groups.
|No effect: No significant differences.||No effect: No significant differences between dietary groups in biomarkers of metabolism (fasting glucose and insulin).||Not analyzed|
|Lindeberg et al. 2007 ||PD vs. CD (Mediterranean)|
| ischaemic heart disease plus either glucose intolerance or type 2 diabetes|
PD: 65 ± 10
CD: 57 ± 7
short-term (12 weeks)
|Positive: weight loss and a decrease in WC.||Not analyzed||Not analyzed||Positive: improving glucose tolerance.||Not analyzed|
|Masharani et al. 2015 ||PD vs. CD (ADA)|
| type 2 diabetes patients|
PD: 58 ± 8
CD: 56 ± 13
short-term (2 weeks)
The average BM changes were similar in both groups without caloric restriction.
|Positive: The PD group had statistically significant declines in TC, HDL, and LDL.||No effects:|
The mean BP did not significantly change in any of the two groups.
|Positive: PD group had greater benefits on glucose control, with significant improvement in insulin sensitivity.||Not analyzed|
|Mellberg et al. 2014 ||PD vs. CD (NNR)|
|, (after 6 m. 61, after 2 y: 49) overweight postmenopausal women|
PD: 59.9 ± 5.5
CD: 60.3 ± 5.9
short-term (6 months);
long-term (24 months)
Both groups significantly decreased FM at 6 months and 24 months, with a more pronounced loss in the PD at 6 months but not at 24 months. WC and SAG also decreased in both the groups, with a more pronounced decrease in the PD at 6 months.
TG levels decreased significantly more at 6 and 24 months in the PD than in the NNR. LDL and TC decreased at both 6 and 24 months, HDL increased in 24 months.
|Positive: decreased in both 6 and 24 mons: DBP, SBP, HR.||No effect:|
No differences were measured over time or between groups with regard to fasting glucose and fasting insulin concentrations and tissue plasminogen activator activity.
|Otten et. al. 2016 ||PD vs. CD|
| healthy, overweight/obese postmenopausal women|
PD: 61 ± 6
CD: 66 ± 2
short-term (6 months);
long-term (24 months)
Both diet groups decreased their BM, BMI, WC, and FM. At 6 months, the PD group showed a greater effect than the LFD group. The LFD lost less LBM compared with the PD. At 24 months, there were no significant differences in body composition between diet groups except for the better preservation of LBM in the LFD group.
TGs, TC, and LDL improved significantly more in the PD group during the first 6 months of the study. At 24 months, both study groups showed an improvement of HDL.
SBP improved in both study groups at 6 months. DBP improved only in the PD group.
HOMA-IR improved significantly after 6 months. Between 6 and 24 months, hepatic insulin sensitivity deteriorated significantly in the PD group with a similar trend in the LFD group.
|Österdahl et al. 2008 ||PD vs. CD (normal diet)|
| healthy volunteers|
30 ± 10
short-term (3 weeks)
Mean BM and WC decreased.
|Partially positive: Decreased SBP||No effects:|
|Pastore et. al. 2015 ||PD vs. CD (AHA)|
4 months CD, followed by 4 months PD;
| hypercholesterolemic patients|
53 ± 7
short-term (4 months)
PD induced a significant BM loss, compared with AHA.
PD significantly lowered mean TC, LDL, and TG and increased HDL.
|Not analyzed||Not analyzed||Not analyzed|
|Stomby et al. 2015 ||PD vs. CD (NNR)|
| overweight and obese|
short-term (6 months)
long-term (24 months)
At 6 months, the PD group had a greater
reduction of BM, BMI, and FM. At 24 months, there were no significant differences in anthropometric measurements between the groups.
TC decreased after 6 months but was unaltered at 24 months compared with baseline. TGs and LDL decreased throughout the intervention, whereas HDL increased after 24 months. There were no group differences in blood lipids.
SBP and DBP decreased at 6 months but had increased to baseline levels after 24 months. There were no group differences in blood pressure.
Fasting serum insulin and HOMA-IR decreased at 6 months
but was unaltered after 24 months. There were no group differences, fasting serum insulin, and HOMA-IR.
|Otten et al. 2017 ||PD vs. PD-EX|
a combination of aerobic exercise and resistance training in 1 h sessions three times weekly)
| individuals with type 2 diabetes with BMI 25–40 kg/m2|
short-term (12 weeks)
|Positive: Both groups showed decreases in BM, FM and WC, without differences between intervention groups. Male participants decreased their WC more in the PD group compared to the PD-EX. Males in the PD-EX group retained more LBM than males in the PD group.||Partially positive:|
TG decreased in both study groups, while the HDL and LDL levels remained unchanged throughout the intervention.
Blood pressure decreased during the study in both intervention groups without any group difference.
Insulin sensitivity and glycemic control improved in both groups, without a difference between groups. The HOMA-IR and revised QUICKI improved in both intervention groups, and the HbA1c decreased during the study in both the PD group and the PD-EX group.
The VO2max and the ergometer cycling workload increased during the study in the PD-EX group, but not in the PD group.
Resting HR decreased more in the PD-EX group than the PD group.
|Otten et al. 2018 ||PD vs. PD-EX|
(PD-EX: aerobic exercise/resistance training in 1 h sessions 3 times weekly)
| individuals with type 2 diabetes with BMI 25–40 kg/m2|
short-term (12 weeks)
|Positive: Both study groups showed a BM, BMI, FM loss.||Positive:|
TG decreased in both gropus
|Not analyzed||Positive: Both groups improved their peripheral and adipose tissue insulin sensitivity, but not their hepatic insulin sensitivity.||Partially positive: The VO2max increased in the PD-EX group only.|
|Otten et al. 2019 ||PD vs. PD-EX|
(exercise training 3 h per week)
| overweight and obese subjects with type 2 diabetes mellitus|
short-term (12 weeks)
significant decreases in both groups in terms of BM, BMI, WC
The PD-EX group showed significant decreases in myocardial TG levels.
These variables were unchanged in the PD group.
There were significant decreases in both groups in terms of fasting triglycerides.
significant decreases in both groups in terms of SBP and DBP.
|Positive: significant decreases in both groups in terms of fasting glucose, HbA1c, fasting insulin, and HOMA-IR.||Partially positive|
The VO2max increased significantly in both groups, although the increase in the PD-EX group was more pronounced. Mean resting HR decreased and the W max. increased significantly in the PD-EX group, while no changes were seen for these measures in the PD group.
|Markofski et al. 2019 ||PD pre vs. post|
| overweight, physically inactive but otherwise healthy adults|
32.7 ± 4.9
short-term (8 weeks)
|Positive: time effect pre- to post-intervention for BM and BMI.||Not analyzed||No effect:|
SBP and DPB were unchanged following the PD intervention.
|Not described||Not analyzed|
|Ryberg et al. 2013 ||PD pre vs. post|
higher energy intake before intervention
| healthy, nonsmoking postmenopausal women with|
BMI > 27 kg/m2
short-term (5 weeks)
BMI, waist and hip circumference, waist/hip ratio, and SAG also decreased significantly.
TC, TG, HDL, LDL, and LDL/HDL decreased significantly.
DBP and resting HR decreased significantly.
Fasting serum glucose and HOMA indices decreased significantly. Insulin sensitivity did not change.
|Smith et al. 2014 ||PD pre vs. post|
subjects completed a CrossFit-based exercise program while adhering to the Paleo diet.
| healthy population|
short-term (10 weeks)
|Positive: FM percentage decreased significantly, as did BM.||Partially positive: A significant increase in non-HDL, LDL, TC/HDL, and TC in healthy subjects following a PD. Deleterious changes were found in those with optimal HDL, non-HDL, TC/HDL, and LDL whereas those within sub-optimal stratifications showed no significant change.||Not analyzed||Not analyzed||Positive:|
significantly increasing the VO2max, a common measure of cardiorespiratory fitness
|BM (kg)||BMI (kg/m2)||WC (cm)||FM (kg)||FM (%)|
|BM (kg)||BMI (kg/m2)||WC (cm)||FM (kg)||FM (%)|
|TC (mg/dL)||TG (mg/dL)||HDL-C (mg/dL)||LDL-C (mg/dL)|
|TC (mg/dL)||TG (mg/dL)||HDL-C (mg/dL)||LDL-C (mg/dL)|
|SBP (mmHg)||DBP (mmHg)||HR (bpm)|
|SBP (mmHg)||DBP (mmHg)|
|fP Glucose (mmol/L)||fP Insulin (mmol/L)||HOMA-IR||HbA1c (%)|
|fP Glucose (mmol/L)||fP Insulin (mmol/L)||HOMA-IR|
|VO2max (mL/kg/min)||VO2max (L/min)||Maximum Workload (W max)|
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