Summary Points
-
Two ounces of pistachio nuts per day for 4 months in prediabetic individuals significantly decreased fasting blood glucose and insulin resistance compared to the control group.
- No significant differences were found in lipid profiles between the pistachio-rich diet and control groups.
By Traci Pantuso ND, MS
Adjunct Faculty, Bastyr University, Seattle; Owner, Naturopathic Doctor Harbor Integrative Medicine, Bellingham, WA
Dr. Pantuso reports no financial relationships relevant to this field of study.
Synopsis: This study is a randomized, crossover clinical trial demonstrating that a pistachio-rich diet significantly reduced fasting glucose, insulin, and insulin resistance compared to the control diet group in prediabetic individuals.
Source: Hernandez-Alonso P, et al. Beneficial effect of pistachio consumption on glucose metabolism, insulin resistance, inflammation, and related metabolic risk markers: A randomized clinical trial. Diabetes Care 2014;37:3098-3105.
Some accumulating evidence serves as a prelude to this study. For example, nut consumption has been associated with a reduced risk of coronary heart disease (CHD) and diabetes, and both conditions are interdependent and possibly inflammatory in nature.1-3 Lifestyle modifications including dietary changes, such as the Mediterranean diet, have demonstrated efficacy in reducing both diabetes and cardiovascular disease (CVD) risk factors.1-4 Nuts and extra virgin olive oil (EVOO) are important components of the Mediterranean dietary pattern.2,3 Much of the evidence for nut consumption relaying health benefits has been in relation to CVD, but less so for diabetes and metabolic syndrome.1-4
The evidence of nut consumption in relation to diabetes risk is slightly more ambiguous than that for CVD.1,3 A number of large studies have investigated the role of nut consumption and diabetes risk. The PREDIMED study included 3541 participants who were at high risk for CVD because they either had type 2 diabetes (T2DM) or had at least three or more risk factors.5 There was a 30% risk reduction for T2DM in the Mediterranean diet groups compared to the control diet.5 The Nurse’s Health Study demonstrated an inverse relationship between women who consumed nuts and T2DM risk.6 A Chinese cohort study of 64,000 women found a protective effect of nut consumption on diabetes risk, while the Iowa Women’s Health Study found that postmenopausal women did not receive a diabetes risk reduction.1 Interestingly, the authors of the Nurse’s Health Study reanalyzed data stratifying for menopausal status and found that the relative risk did not change significantly and that nut consumption continued to show a protective effect.1 Another study, which did not demonstrate a protective effect of nut consumption on diabetes risk, was the Physicians’ Health Study with 20,224 male participants.7
Recent study findings demonstrated decreased post-prandial glucose levels when people consumed pistachios with carbohydrates.8 Pistachio intake has also been shown to decrease LDL and other inflammatory markers in healthy individuals and those with metabolic syndrome.9 The authors of this study sought to investigate whether a pistachio-rich diet would improve glucose metabolism and insulin levels in prediabetic individuals.
Community-dwelling women and men between 25-65 years of age, body mass index (BMI) < 35 kg/m2, and a fasting glucose between 100-125 mg/dL were recruited from primary care centers affiliated with the Universiari Hospital of Saint Joan de Reus in Spain. Exclusion criteria included medical, dietary, or social conditions that hinder compliance; significant hepatic, renal, or endocrine disease; pregnant or desiring to become pregnant within the study time frame; vegetarian or hypocaloric diet for weight loss; bad dentures making it difficult to chew pistachios; alcohol, tobacco, or drug abuse; diabetes or using oral antidiabetic agents; frequent consumption of nuts or known allergy; use of multivitamins, vitamin E, and other antioxidant supplements; and use of plant sterols, fish oil supplements, or psyllium.
The design of this study was a randomized, crossover clinical trial that started with a 15-day run-in period, then a 4-month treatment period of either control diet (CD) or pistachio-supplemented diet (PD), followed by a 2-week washout period prior to the next 4-month CD or PD intervention. During the 2-week washout period before each 4-month diet intervention, the participants followed a normocaloric diet containing 50% of energy as carbohydrates, 15% as protein, and 35% as total fat. Three-day dietary records were used to estimate dietary intake at the beginning of each 4-month trial and every 2 months after. Dietary instructions were provided to the participants in each group. These included seasonal recipes and biweekly menus after the 2-week run-in period and then monthly until the completion of the 4-month intervention period.
During the intervention, the PD group participants supplemented with 2 ounces (57 grams or approximately one-half cup) of pistachio nuts that were given to the participants at no cost. The pistachio nuts were roasted, and half of them were salted. The diet of the CD group was adjusted with additional fat to equal the PD group with the addition of increased fatty foods that mostly consisted of olive oil.
Physical examinations consisting of weight, waist circumference, and body mass index occurred at baseline, 2-week run-in, and then monthly until the end of each 4-month intervention period. Body composition was measured with bioelectrical impedance analysis at the beginning and end of each 4-month trial. Blood pressure was measured as well.
To measure adherence to the PD, empty pistachio packets were counted and plasma levels of lutein-zeaxanthin and γ-tocopherol levels were measured using liquid chromatography. Physical activity was calculated using the Spanish version of the Minnesota Leisure Time Physical Activity Questionnaire, which is a validated questionnaire. Gastrointestinal side effects were evaluated through a questionnaire.
At baseline and the end of the 4 months, blood was analyzed for:
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Fasting glucose, serum lipid profiles, LDL-c, oxidized LDL, soluble receptor for advanced glycation end products, insulin, leptin,
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Insulin resistance and insulin secretion were calculated with the homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) and HOMA of beta-cell function (HOMA-BCF) methods.
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Plasma tissue factor, thromboxane B2, interleukin-18, interleukin-6 (IL-6), plasma fibrinogen, von Willebrand factor, platelet factor 4, gastric inhibitory polypeptide, GLP-1, C-peptide, adiponectin, plasminogen activator inhibitor-1 (PAI-1), and resistin.
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To evaluate glucose uptake in cells, peripheral lymphocytes were obtained from venous blood samples. The lymphocytes were incubated with deoxy-D-glucose that was then measured through fluorescence inside the lymphocytes after 30 minutes.
- Gene expression analysis of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), solute carrier family 2 (SLC2A3, SLC2A4), IL-6, RETN were measured by real-time polymerase chain reaction (RT-PCR).
All statistical analyses were performed using intent-to-treat (ITT) and per-protocol (PP) approaches. ITT analysis included all randomized participants at the time after completion of baseline measurements. PP analysis excluded participants who did not complete the last visit.
One hundred and eight participants were screened for eligibility and 54 participants were randomly assigned to an intervention sequence. Five of the 54 participants dropped out of the study during the pistachio intervention for personal reasons. Baseline characteristics were similar among the participants, except that men had significantly higher weight and waist circumferences than the women. No significant differences in the study groups were noted at baseline.
During the PD intervention, glucose and insulin levels decreased significantly compared to baseline (see Table 1). The control group did not demonstrate a significant difference between baseline and the CD intervention (see Table 1). The HOMA-IR value also significantly decreased in the PD group from baseline compared to the CD group (see Table 1). No significant difference in the HOMA-BCF score or hemoglobin A1c was found in either group. No significant differences were found in lipid profiles between groups (see Table 2). There was, however, a nonsignificant decrease found in LDL measurement compared to baseline in the PD group. In the CD group, there was a small non-significant increase in the LDL compared to the baseline value. Plasma IL-6 and RETN were not significantly different in the PD group compared to the CD group.
|
Table 1: Treatment Dosages of Artemisia annua |
||||
|
Low-dose WPAA |
High-dose WPAA |
Low-dose artemisinin |
High-dose artemisinin |
|
|---|---|---|---|---|
|
P. yoelii inoculated mice |
40 mg (24 mg |
200 mg (120 mg |
600 mcg of A (24 mg artemisinin per kg) |
3000 mcg of A (120 mg artemisinin per kg) |
Table 2: Lipid Profile Measurements in PD and CD Groups
|
Variable |
PD BaselineMean (95% CI) |
PD Change Mean (95% CI) |
CD Baseline Mean (95% CI) |
CD Change Mean (95% CI) |
Treatment Effect P-value |
|---|---|---|---|---|---|
|
Total |
217.44 |
-3.74 |
213.83 |
2.11 |
0.15 |
HDL (mg/dL) |
54.28 |
1.33 |
54.42 |
1.34 (0.71,3.39) |
0.96 |
|
LDL (mg/dL) |
137.93 |
-4.00 |
136.77 |
1.20 |
0.16 |
|
VLDL (mg/dL) |
25.19 |
-1.04 |
22.74 |
0.36 |
0.28 |
|
Total |
4.29 |
-0.19 |
4.14 |
-0.05 |
0.31 |
|
LDL/HDL ratio |
2.78 |
-0.15 |
2.68 |
-0.04 |
0.33 |
|
Triglycerides (mg/dL) |
125.81 |
-4.96 |
113.89 |
7.47 |
0.15 |
In lymphocytes, a significant decrease in the uptake of glucose was detected in the PD group (-78.78% [127.46, -30.10]) compared with the CD group (15.86% [-34.55, 66.27], P = 0.01). In previous studies, increased glucose uptake in peripheral blood mononuclear cells has been shown to lead to immune hyperactivity.10 Fibrinogen and PF-4 were significantly decreased in the PD group compared to the CD group. GLP-1 increased during the pistachio diet compared with the CD. IL-6 messenger ribonucleic acid (mRNA) in the PD group was decreased compared with the CD group by 9% (P = 0.004). RETN gene expression was also significantly decreased in the PD group compared to the CD group (P = 0.04). To measure the facilitated glucose transporter gene expression, SLC2A3 and SLC2A4 gene expression was measured. SLC2A3 expression was not significantly different between groups. SLC2A4 expression were significantly increased by 69% in the CD group compared to the PD group (P = 0.03). SLC2A4 protein has been found to be increased in diabetics and individuals with impaired glucose metabolism in lymphocytes. TLR gene expression was not significantly different between groups.
There were no gastrointestinal side effects observed during the trial, and no changes in medication occurred during the study.
Commentary
This study found that consumption of 2 ounces of pistachio nuts per day for 4 months by individuals with prediabetes decreased fasting plasma glucose levels and insulin resistance. Interestingly, total cholesterol did not decrease, which has been demonstrated in other studies investigating the effects of nut consumption.11 The authors mention that the reason there were no significant differences in the lipid profiles may be due to differences in lipid metabolism in prediabetic individuals. Furthermore, the CD group diet contained EVOO, which has lipids effects. EVOO also may have anti-inflammatory effects, explaining why some of the parameters investigated were not different between the groups.2 This EVOO effect may be important especially if the inflammatory and lipid metabolism are abnormal in prediabetic participants, and the differences may have been too small to detect with the power analysis used.
This study also demonstrated that IL-6 mRNA was decreased in the PD group compared to the CD group; however, plasma IL-6 protein levels were not significantly different between groups. Also, the facilitated glucose transporter gene SLC2A4 mRNA was 69% higher in the CD group compared to the PD group. More research is required for the IL-6 and SLC2A4 findings to be able to be applied clinically.
There are a number of strengths of this study, including the crossover, randomized design, which controlled for individual variability. This study also used the dietary compliance markers of plasma lutein–zeaxanthin and γ-tocopherol levels to evaluate pistachio intake, an effective method to quantify intake. The study duration for the treatment period was likely adequate; 4 months is a “medium” duration, which should pick up some effects. That said, a longer study duration is warranted to further understand the effects of a PD.
Limitations of this study include the small number of participants and the limited study demographic. Due to varying physiology, effects on people with prediabetes may not extrapolate to people with diabetes or, for that matter, healthy adults.
Another limitation of this study is the source of the funding as it was funded by the American Pistachio Growers and Paramount Farms. The authors state, “None of the funding sources played a role in the design, collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication.”
In summary, this study adds further evidence that the addition of nuts to the diet, in particular pistachios, is a safe nutritional strategy to improve metabolic risk factors in people with prediabetes. Nuts are also a good dietary recommendation for healthy individuals to prevent cardiovascular disease and are recommended by the American Heart Association and the U.S. Department of Agriculture. Nuts are a nutrient-dense food, high in protein, fiber, total fat, and plant sterols, the latter of which is known to slow or inhibit cholesterol absorption from the intestinal lumen. Nuts are also good sources of calcium, magnesium, potassium, folate, and antioxidants. Research has demonstrated that although nuts are high in fat, consuming a moderate amount will not cause weight gain.1 Pistachios are higher in ß-carotene, γ-tocopherol, and lutein than other nuts, making them a good source of antioxidants. Recommending a healthy diet such as the Mediterranean diet pattern with nuts is a safe and effective nutritional strategy to prevent diabetes and cardiovascular disease and improve insulin resistance.
REFERENCES
- Ros E. Health benefits of nut consumption. Nutrients 2010;2:652-682.
- Urpi-Sarda M et al. Virgin olive oil and nuts as key foods of the Mediterranean diet effects on inflammatory biomarkers related to atherosclerosis. Pharmacological Research 2012;65:577-583.
- Ros E. Nuts and novel biomarkers of cardiovascular disease. Am J Clin Nutr 2009;89:1649S-1656S.
- Fraser GE, et al. A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study. Arch Intern Med 1992;152:1416-1424.
- Salas-Salvado J, et al. Prevention of diabetes with Mediterranean diets. Ann Intern Med 2014;160:1-10.
- Jiang R, et al. Nut and peanut butter consumption and risk of type 2 diabetes in women. JAMA 2002;288:2554-2560.
- Kochar J, et al. Nut consumption and risk of type II diabetes in the Physicians’ Health Study. Eur J Clin Nutr 2010;64:75-79.
- Kendall CWC, et al. Acute effects of pistachio consumption on glucose and insulin, satiety hormones and endothelial function in the metabolic syndrome. Eur J Clin Nutr 2014;68:370-375.
- Bullo M, et al. Dietary regulation of glucose metabolism in metabolic syndrome. Curr Vasc Pharmacol 2013;11:928-945.
- Oleszczak B, et al. The effect of hyperglycemia and hypoglycemia on glucose transport and expression of glucose transporters in hyman lymphocytes B and T: An in vitro study. Diabetes Res Clin Pract 2012;96:170-178.
- Casas-Agustench P et al. Effects of one serving of mixed nuts on serum lipids, insulin resistance and inflammatory markers in patients with the metabolic syndrome. Nutr Metab Cardiovasc Dis 2011;21:126-135.
This study is a randomized, crossover clinical trial demonstrating that a pistachio-rich diet significantly reduced fasting glucose, insulin, and insulin resistance compared to the control diet group in prediabetic individuals.
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