Are fatty nuts a weighty concern? A systematic review and meta-analysis and dose–response meta-regression of prospective cohorts and randomized controlled trials. Stephanie K. Nishi, Effie Viguiliouk, Sonia Blanco Mejia, Cyril W. C. Kendall, Richard P. Bazinet, Anthony J. Hanley, Elena M. Comelli, Jordi Salas Salvadó, David J. A. Jenkins, John L. Sievenpiper. Obesity Reviews, September 8 2021. https://doi.org/10.1111/obr.13330
Summary: Nuts are recommended for cardiovascular health, yet concerns remain that nuts may contribute to weight gain due to their high energy density. A systematic review and meta-analysis of prospective cohorts and randomized controlled trials (RCTs) was conducted to update the evidence, provide a dose–response analysis, and assess differences in nut type, comparator and more in subgroup analyses. MEDLINE, EMBASE, and Cochrane were searched, along with manual searches. Data from eligible studies were pooled using meta-analysis methods. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Certainty of the evidence was assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Six prospective cohort studies (7 unique cohorts, n = 569,910) and 86 RCTs (114 comparisons, n = 5873) met eligibility criteria. Nuts were associated with lower incidence of overweight/obesity (RR 0.93 [95% CI 0.88 to 0.98] P < 0.001, “moderate” certainty of evidence) in prospective cohorts. RCTs presented no adverse effect of nuts on body weight (MD 0.09 kg, [95% CI −0.09 to 0.27 kg] P < 0.001, “high” certainty of evidence). Meta-regression showed that higher nut intake was associated with reductions in body weight and body fat. Current evidence demonstrates the concern that nut consumption contributes to increased adiposity appears unwarranted.
4 DISCUSSION
The present systematic review and meta-analysis of nut consumption and adiposity involving six prospective cohort studies and 86 RCTs (114 trial comparisons) did not illustrate an increased risk of overweight/obesity or raise other measures of adiposity studied in adults.
Based on the long-term findings from the prospective cohort studies, a significant inverse association was observed across outcomes assessed. These findings align with those proposed by the systematic review of prospective studies by Eslami and colleagues.35 Suggesting that nut consumption may have a protective effect on risk of adiposity accumulation. This is further supported by the results of the present aggregate analyses from the RCTs, which showed a lack of a causal effect of nut consumption on the reported measures of adiposity. Previous systematic reviews and meta-analyses of trials involved differing inclusion and exclusion criteria yet showed similar findings in regard to a lack of effect of nut consumption on body weight, BMI, or waist circumference.36, 37 The lack of effect of nut consumption on waist circumference is further supported by Blanco Mejia and colleagues in their systematic review and meta-analysis assessing nuts and metabolic syndrome.3
Significant heterogeneity in the current analysis did exist. While this heterogeneity could not be adequately assessed categorically for the cohorts as there were too few cohort studies, subgroup analyses and meta-regression of the trials identified potential sources of heterogeneity. For the trials, similar to the previous publications,36, 37 energy balance was identified as a potential source of heterogeneity. However, in the current analysis, incorporating nuts into a dietary pattern involving an overall negative energy balance compared to a negative energy balance without nuts was observed to favour nuts in regard to not increasing body weight, BMI, or waist-to-hip ratio. Inclusion of nuts as a part of a dietary pattern without concern for increased body weight or adiposity measures is further supported by findings from the PREDIMED trial, where inclusion of nuts as part of a Mediterranean dietary pattern saw slightly reduced body weight and adiposity measures with no significant differences when compared with the Mediterranean dietary pattern with olive oil or the low fat dietary pattern.144 A sensitivity analysis involving the inclusion of the PREDIMED trial did not significantly affect the magnitude or direction of the current findings. In addition to energy balance, nut dose was detected as a potential effect modifier of body weight and body fat, where greater reductions were observed with increasing nut dose. In categorical analyses, nut doses ≥45.5 g/day indicated lower adiposity measures compared to lower doses. As nut doses of 1 to 1.5 ounces (~28 to 42.5 g) per day are often noted in dietary guidelines, as well as the FDA qualified health claim for coronary heart disease risk reduction, this suggests the provision often seen following nut recommendations, as well as stated at the end of the applicable qualified health claims asserting “see nutrition information for fat [and calorie] content” with the implied message that foods high in fat and calories lead to increased adiposity may be unwarranted.17-19 Likewise, continuous linear meta-regression identified dose-dependent relationships between nut consumption with both body weight and body fat, where nut dose was inversely correlated with body weight and fat. However, significant departures from linearity were observed in BMI, waist circumference, and waist-to-hip ratio, where the maximum protective dose appeared to be around 50 g/day based on waist-to-hip ratio. Although the waist-to-hip ratio may have been confounded by the nonsignificant positive correlation observed between waist circumference and nut consumption. This positive association between nut consumption and waist circumference differs from findings in the literature, where nut and seed consumption has been associated with significantly decreased pericardial fat, and trends toward decreased visceral fat,145 and monounsaturated fat intake, which is prevalent in nuts, compared to carbohydrate intake has been shown to prevent central fat redistribution.146
4.1 Strengths and limitations
Strengths of the present systematic review and meta-analysis include its comprehensive design, comprising both prospective cohort studies and RCTs, using the GRADE approach to evaluate the certainty of evidence. The prospective cohort studies provide assessment of nut consumption over the long term in a large sample of participants in free-living conditions in relation to adiposity. The design of RCTs provides the best protection against bias; there were also a substantial number of trials identified (106 trial comparisons) for the primary outcome of body weight; the median follow-up period was 8 weeks, which allows for the assessment of a moderate duration of intervention. In addition, the meta-regression and subgroup analyses provide further insight as to various factors that have previously been hypothesized to influence the impact of nut consumption on adiposity.
These analyses are not without limitations. For the prospective cohort studies, we downgraded the certainty of the evidence for serious inconsistency in the estimates across the studies for body weight change as there was evidence of unexplained heterogeneity (92%). Although the inconsistency may have related to measurement error as there was a lack of repeated measurement of intake of nuts, use of a food frequency questionnaire measure that was not specifically validated for nut intake, and adiposity measures were mainly self-reported by participants. Risk of bias was also observed for body weight change as participants were primarily comprised of well-educated individuals, many of whom were health professionals, including university graduates from SUN and health professionals recruited from NHS, NHS II, and HPFS, and thus may not be generalizable to other populations.
For the RCTs, we downgraded the certainty of evidence for serious inconsistency in the estimates due to unexplained heterogeneity in all the outcomes assessed, except BMI. Subgroup analyses indicated potential sources of heterogeneity; however, this was often observed when the covariate was unevenly distributed, as well as the differences in treatment effects between subgroups are unlikely to otherwise alter clinical decisions.
Weighing these strengths and limitations using GRADE, the certainty of evidence ranged from “very low” to “high.” A reason for the “very low” certainty of evidence observed is due to the GRADE approach starting observational studies at “low” certainty. Overall, the prospective cohort studies showed mostly “moderate” and the RCTs showed equally “high” and “moderate” certainty of evidence.
4.2 Potential mechanisms of action
There are several biological mechanisms which may explain the association, more specifically, the lack of association observed between nut consumption with overweight/obesity risk and other measures of adiposity, including: (1) unsaturated fatty acid content, (2) satiating effect, and (3) physical structure, each in a way associated with the bioavailability of nuts when consumed. Nuts are rich in unsaturated fatty acids (monounsaturated fatty acids [MUFAs] and polyunsaturated fatty acids [PUFAs]), which are suggested to be more readily oxidized147 and have a greater thermogenic effect148 compared to saturated fatty acids, leading to less fat accumulation. Nuts are also rich in protein and fiber and dietary components associated with increased satiety.149-151 In addition to the protein and dietary fiber content of nuts, the physical structure may also contribute to their satiating effect since the mastication process involved in mechanically reducing nuts to a particle size small enough to swallow activates signaling systems that may modify appetite sensations.152 The physical structure of nuts may also contribute to fat malabsorption due to the fat content in nuts being contained within walled cellular structures that are incompletely masticated and/or digested.153-156 Thus, due to these biological mechanisms which may be associated with decreased bioavailability, the Atwater Factor, a system for determining the energy value of foods which was founded over a century ago, associated with nuts, may overestimate the calories obtained by the body from nut consumption by approximately 16% to 25% depending on the nut type and form.157-159 This may potentially explain the present findings of a protective effect of nut consumption on measures of adiposity.
4.3 Practical implications
Current clinical practice guidelines already suggest the incorporation of nuts for the improvement of glycemic control and cardiovascular risk factors; however, there are often qualifiers regarding their fat content and energy density.14-16 With overweight and obesity respectively affecting 39% and 13% of adults globally and increased adiposity being a modifiable risk factor for diabetes and cardiovascular diseases, body weight management is an important consideration in dietary and lifestyle recommendations.160 Evidence from this systematic review and meta-analysis suggests that nuts may continue to be highlighted as a nutrient dense component of dietary patterns for their cardiometabolic benefits without concerns of an adverse effect on weight control. Nuts are currently recommended as part of the Mediterranean, Portfolio, and DASH dietary patterns, yet despite tree nut and peanut intake increasing over the past 10 years, intake worldwide remains low at an estimated 16.7 g/day with about 15.2 g being contributed by peanuts.20 This is far below current recommendations of 1 to 1.5 ounces per day (approximately 28.3 to 42.5 g/day).6, 17-19 Based on the median nut intake in the trials of the current analyses and FDA qualified health claims, a dose of 42.5 g/day of nuts could easily be integrated into a daily dietary pattern by incorporating them into meals and/or consuming them as snacks. Except for individuals with nut allergies, no increase in side effects compared with control groups was reported in any of the cohort studies or trials, suggesting that dietary patterns which incorporate nuts as a regularly consumed component are safe. Future research may further assess the impact of different varieties of nuts and formats in which they may be consumed and how they are incorporated into the diet.