Almond supplementation reduces serum uric acid in coronary artery disease patients

12 Pages·2017·0.54 MB·English

by  Humaira Jamshed

Jamshedetal.NutritionJournal (2016) 15:77
DOI10.1186/s12937-016-0195-4
SHORT REPORT Open Access
Almond supplementation reduces serum
uric acid in coronary artery disease
patients: a randomized controlled trial
Humaira Jamshed1, Anwar-ul-Hassan Gilani1,2*, Fateh Ali Tipoo Sultan3, Faridah Amin1, Jamshed Arslan1,
Sumaira Ghani1 and Madiha Masroor1
Abstract
Objective: Elevated serum uric acid (UA), a biomarker of renal insufficiency,is also an independent prognostic
marker for morbidity incoronary artery disease (CAD) and poses serious health risks. This study reports the effect of
almond consumption onUA inCAD patients.
Study design:A randomized controlled clinical trial was conductedwith three groups: no-intervention(NI),
Pakistani almonds (PA) or American almonds (AA). Patients were recruited from the Cardiology Clinics, Aga Khan
University Hospital. Twofollow-ups were scheduled atweek-6 and week-12.150 patients were randomly divided in
threegroups (50 per group). NI was not given almonds, whereas thePA and AA were given Pakistani and American
almond varieties (10 g/day),respectively;with instruction to soak overnight and eat before breakfast.
Results: Almonds supplementation significantly reduced (p<0.05) serum UA among groups, and over time. At
week-6, UA concentrationswere -13 to -16% less inPA and AA; at week-12 the concentrations were -14 to -18 %
less, compared to NI. Systolic and diastolic blood pressure and body weightsof theparticipants remained fairly
constant among all thegroups.
Conclusion: Almonds (10 g/day),eaten before breakfast, reduces serum UA inCAD patients. Prevention of
hyperuricemia can confer protection from kidney and vascular damage and ifextrapolated for general population,
dietary almonds can offergrander health benefit.Trial is registered atAustralian NewZealand Clinical trial registry
as ACTRN12614000036617.
Keywords: Hyperuricemia, Coronary artery disease, Nuts, Soaked almonds, Lowdose
Introduction infarction or stroke [4]. An increase in serum UA by
There has been considerable increase in global preva- 1 mg/dL contributes to 12 % increase in risk of CAD
lence of hyperuricemia, in the past few years, backed by death [5]. This association is believed to be stronger in
western dietary patterns. Where higher serum uric acid women than men [5]. But there are also some indications
(UA) frequently indicates renal insufficiency [1], it may where,inmiddle-agedmen,hyperuricemiaservedasarisk
also be associated with coronary artery disease (CAD) factorforcardiovascularandall-causemortality[6].
[2],and deliberated asaprognosticmarker formorbidity UAisshowntopossessanti-oxidantpotential[7],which
andmortality, independentofotherrisk factors [3].Even undermines its causative role in chronic diseases. Yet, its
inpatientswithnohistoryof heartdiseaseorstroke,ele- establishment as a comorbid risk marker is backed by re-
vated UA was associated with higher risk of myocardial cent meta-analysis [8] and systemic review [5] showing
significant correlation between hyperuricemia and CAD.
*Correspondence:[email protected];[email protected] Further signifying its role for cardiovascular health,
1DepartmentofBiologicalandBiomedicalSciences,AgaKhanUniversity, are the studies where anti-hypertensive and/or lipid-
Karachi,Pakistan
2PakistanCouncilforScienceandTechnology,GovernmentofPakistan, neutralizing therapies limited UA production, thereby
Shahara-i-Jamhuriat,G-5/2,Islamabad,Pakistan reducing CAD mortality [9, 10].
Fulllistofauthorinformationisavailableattheendofthearticle
©2016TheAuthor(s).OpenAccessThisarticleisdistributedunderthetermsoftheCreativeCommonsAttribution4.0
InternationalLicense(http://creativecommons.org/licenses/by/4.0/),whichpermitsunrestricteduse,distribution,and
reproductioninanymedium,providedyougiveappropriatecredittotheoriginalauthor(s)andthesource,providealinkto
theCreativeCommonslicense,andindicateifchangesweremade.TheCreativeCommonsPublicDomainDedicationwaiver
(http://creativecommons.org/publicdomain/zero/1.0/)appliestothedatamadeavailableinthisarticle,unlessotherwisestated.
Jamshedetal.NutritionJournal (2016) 15:77 Page2of5
Almonds are among the nuts approved by Food and provided. Compliance was monitored through regular
Drug Administration – United States to have the poten- phone calls (twice per week). Follow-up visits were
tial of reducing CVD risk [11]. The lipid-neutralizing scheduled at week-6 and week-12 (±3 days), at which
properties, among others, have been extensively elabo- blood samples were collected and vitals were recorded.
rated [12]. Dietary supplementation of almonds is shown Participants ofNI received almondsafter the completion
to prevent hyperuricemia in a cardiovascular disease rat oftrial.
model [13]. This study inspects the UA-reducing poten- Pakistanialmonds,namelyTalwar,growninBalochistan–
tial ofalmondsupplementationinCADpatients. Pakistan; and imported Americanalmonds,locally available
at Utility stores in Karachi, were used. Serum concen-
Methods tration of uric acid (UA) was measured on Roche
Studypopulation Cobass c-111 automated analyzer using commercially
Hundred and fifty CAD patients were recruited from Car- available kit (Uric acid kit no. 4657608190).
diologyClinicatTheAgaKhanUniversityHospital, Kara- DatawereanalyzedonSPSSversion17.0andGraphpad
chi.Theeligibilitycriteriaandtriallogisticshavepreviously Prism, and results are presented as means±SEM. Two-
beendefinedindetail,followingtheCONSORTguidelines way repeated measures ANOVA was used to compare
[14]. Briefly, patients consuming nuts on regular basis means of groups followed by Bonferroni post-tests. For
(>15 g/d; three days/week) or those having nut allergies categorical data, chi-square test was used to compare dif-
were excluded. Informed consent was obtained. Using ferences between groups. P-value<0.05 was considered
blockrandomization,patientswereassignedanyofthefol- statisticallysignificant(95%Confidenceinterval).
lowing three groups: No Intervention (NI); Intervention
withPakistanialmonds(PA)orAmericanalmonds(AA). Results
The flow of participants through the trial, as per CON-
Studydesign SORT format, has been reported previously [14]. Attri-
Approval was obtained from Ethical Review Committee tion rate was around 15 %. The major reasons included:
of The Aga Khan University, Karachi, Pakistan (Applica- failure to contact (n=20); leaving city in summer vaca-
tion ID: 2230-Med-ERC-12), and the trial was registered tions (n=8); and a few cases of angioplasty (n=3). The
at Australian New Zealand Clinical Trial Registry (ID: baselinecharacteristicsofparticipantsineachgroup,ispro-
ACTRN12614000036617). videdinTable1.SystolicanddiastolicBPandbodyweight
Baseline blood was drawn and vitals (body weight, of the participants remained fairly constant (p>0.05)
blood pressure etc.) were recorded. Participants of NI throughout the twelve weeks of the study, as seen in
were instructed not to consume any nuts, specifically al- Table 2.
monds, during their enrollment in trial; whereas partici- Serum UA concentrations were similar at baseline
pants of PA and AA were given almonds (10 g/day), (Table 1), in all the groups (p>0.05). In a male-to-male
with the instruction to consume in a traditional way (i.e. and female-to-female comparison, the data in Table 2
soak overnight, peel and eat before breakfast in the show that in PA group, at week-6, males had -15 % and
morning). Diaries, to record almond consumption, were females had -12 % lower UA than those in NI (p<0.05).
Table1BaselinecharacteristicsofCADpatientsrandomizedintono-intervention,PakistanialmondorAmericanalmondgroups
NoIntervention1 PakistaniAlmonds1 AmericanAlmonds1
Mean SEM Mean SEM Mean SEM
Age,years 61 0.2 57 1.6 61 1.5
Gender
Male,n 39 36 38
Female,n 11 14 12
Bodyweight,kg 73.4 0.2 79 1.9 75 1.6
BloodPressure,mmHg
Systolic 127 0.4 126 2.4 128 2.6
Diastolic 70 0.2 67 1.2 68 1.3
SerumUricAcid,mg/dL
Male 7.2 0.49 6.9 0.23 6.8 0.22
Female 5.9 0.34 5.7 0.14 5.6 0.21
1n=50pergroup
Jamshedetal.NutritionJournal (2016) 15:77 Page3of5
Table2BloodpressureandserumuricacidconcentrationsofCADpatientsrandomizedintono-intervention(NI),Pakistanialmonds
(PA)andAmericanAlmonds(AA)groups,atweek-6andweek12
NoIntervention PakistaniAlmonds AmericanAlmonds
Male Female Male Female Male Female
n=25 n=9 n=27 n=11 n=33 n=8
Mean SEM Mean SEM Mean SEM Mean SEM Mean SEM Mean SEM
BloodPressure
Systolic,mmHg Week6 128 0.5 129 0.6 126 1.7 127 0.9 127 1.7 126 1.4
Week12 126 1.2 127 0.5 124 3.1 126 1.2 125 3.4 125 0.5
Diastolic,mmHg Week6 71 0.3 69 0.4 67 0.5 68 0.5 67 0.2 66 0.8
Week12 70 1.8 69 1.0 66 1.2 67 1.1 67 1.0 67 0.2
UricAcid,mg/dL Week6 7.1 0.2 5.8 0.17 6.0* 0.22 5.1* 0.16 5.9* 0.26 4.7* 0.26
Week12 7.0 0.3 5.8 0.25 5.8* 0.20 4.9* 0.15 5.6* 0.28 4.6* 0.27
*p<0.05comparedtorespectiveNo-Interventioncontrolgroup
At week-12, male and female participants of PA had -17 production; inducing smooth muscle cell proliferation;
and -16 % lower concentrations, respectively, those in anddirectreactionwith,anddepletionofNO.
NI (p<0.05). Table 2 also shows that, at week-6, serum Almondsupplementationisshowntoinfluencesomeof
UA in male and female participants of AA were -17 and these parameters.Although,Jenkinsetal. reportnoeffect
-19%lessthaninNI(p<0.05).Atweek-12,UAwasfur- of almonds onCRP, BP or pulmonary NO [17]; Rajaram
ther reduced up to -20 and -21 % in males and females, et al. [18] observed significant reduction in CRP. Two
respectively,inAA. studies in diabetic patients [19, 20], report a drop in
Figure 1a shows comparison with respect to baseline. CRP accompanied by anti-inflammation via IL-6
At week-6, drop in serum UA concentration in male
(1%)andfemale(2%)participantsofNIwasinsignificant
(p>0.05). In the almonds-intervention groups, there was
a significant(p<0.05)dropinUA;around-13%inmales
of both PA and AA, and -11 and -16 % in females of PA
andAA,respectively.
Figure 1b compares UA concentrations of baseline and
intervention.Atweek-12,therewasnegligible(-3and-2%)
dropinmalesandfemalesofNI,whilethedropinPAand
AAwassignificant (-16and-14% inmalesand femalesof
PAand-18%inbothmalesandfemalesofAA;p<0.05).
Discussion
To the best of our knowledge, this is the first almond-
intervention study on CAD patients reporting UA reduc-
tion. Previously, in rat model, dietary almonds prevented
high-fat diet-induced hyperuricemia, followed by reduced
nitricoxide(NO)productionviaendothelialNOsynthase
(eNOS)inhibitionresultinginimprovedvascularfunction
of isolated aorta [13]. So, from results in CAD patients,
wecanalsoinferprobablevascularprotection.
SerumUAmaybeconsideredasabiomarkerfor vascu-
lar function [15]. Anticipated pathways of UA-induced
vascular dysfunction [16] include, but are not limited to:
pro-oxidative affect, whereby UA decomposes and gener-
ates free radicals; pro-inflammatory affect via association Fig.1Percentagechangeinserumuricacid(UA)frombaseline,at
withbiomarkerslikeinterleukins(IL-1,IL-6,IL-10,IL-18), week-6(a)and week-12 (b), in coronary artery disease patients
tumor necrosis factor (TNF-α) and C-reactive proteins randomizedinno-intervention(NI),Pakistanialmond(PA)orAmerican
almond(AA)groups.Valuesaremean±SEM;n=34inNIgroup,n=38
(CRP); endogenous stimulation of innate immunity; chan-
inPAgroupandn=41inAAgroup
ging expression of endothelin-1; promoting angiotensin-II
Jamshedetal.NutritionJournal (2016) 15:77 Page4of5
reduction; while Liu et al. [20], also reports decrease in refiningthemanuscript.Allauthorshavereadandapprovedthefinal
TNF-αbydietaryalmonds.Bhardwajetal.[21],alsodem- manuscript.
onstrated drop in CRP, accompanied by improved flow-
Competinginterests
mediateddilatation,indicatingimprovedendothelialfunc-
Theauthorsdeclarethattheyhavenocompetinginterests.
tion.Butmorerecently,Chenetal.[22]reportednoeffect
of almond supplementation on vascular function, CRP, Consentforpublication
TNF-αandeventhelipidprofileofCADpatientsinaran- Thewritteninformedconsentsignedbyalltheparticipants,alsoincluded
domized cross-over clinical trial. This may be due to the theconsentforpublication.
drugtherapywhichcouldmimictheeffectofintervention.
Ethicalapprovalandconsenttoparticipate
Decreaseinvascularcelladhesionmoleculeswasobserve,
Thisstudywasconductedaccordingtotheguidelineslaiddowninthe
which may indicate improvement in vascular function. DeclarationofHelsinkiandallproceduresinvolvinghumanpatientswere
Trials longer than four to six weeks may be able to offer approvedbytheEthicsReviewCommittee,AgaKhanUniversity(Application
ID:2230-Med-ERC-12).Writteninformedconsent(inbothlanguagesi.e.
detectible improvements in vascular function of CAD
EnglishandUrdu)wasobtainedfromallpatients.
patients.
Almonds are rich in L-arginine, which is a precursor of Authordetails
1DepartmentofBiologicalandBiomedicalSciences,AgaKhanUniversity,
NO. Supplementation of L-synthetic arginine reverses Karachi,Pakistan.2PakistanCouncilforScienceandTechnology,Government
hyperuricemia-induced hypertension in rats [23]. How- ofPakistan,Shahara-i-Jamhuriat,G-5/2,Islamabad,Pakistan.3Departmentof
ever, BP of participants in our trial remained fairly con- Medicine,AgaKhanUniversity,Karachi,Pakistan.
stant during twelve weeks. Reason being, almost all CAD
Received:28March2016Accepted:2August2016
patientswereonanti-hypertensivemedications,andbase-
lineBPwaswithinnormalranges.
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ALMOND INTERVENTION IN TYPE2DIABETESMELLITUS 99
Indians found an age-adjusted known or diagnosed preva- diet.Almondsfittherequirementsofafooditemthatisnot
lenceof16%,4withmorethan25%ofdiabeticsundiagnosed. onlyculturallytrustedandacceptedforitsnutritionalvalue,21
A 10-year follow-up to the Chennai Urban Rural Epide- but has also been clinically proven to impart the health
miologyStudy(CURES)found26%ofsubjectswithnormal benefits necessary to help manage dysglycemia and its dis-
glucose tolerance converting to prediabetes, and another ease manifestations, which are known to impact cardiome-
20% converting to diabetes, with an overall dysglycemia tabolic health.22–25 Results from these and other successful
conversion rate of 45% and no sex-wise differences ob- clinical studies of almond intervention provide sufficient
served.5 The incidence rate of diabetes in the same study data and confidence to test the effects of almond con-
was79per1000person-years,oneofthehighestreportedin sumption on health outcomes in Indian subjects, despite
a large ethnic group and twice the rate for Caucasians (35– their unique ‘‘Asian Indian’’ phenotype. This study was
40 per 1000 person years).5 Not only is the disease therefore conducted to investigate the effects of daily con-
spreadingatanalarmingrate,butitalsoseemstobecutting sumption of almonds for 24 weeks in T2D subjects, spe-
across all social, demographic, and age groups in India. cifically on measure of glycemia and CVD risk factors.
Initially recognized as a disease of affluent migrants,6
T2D seems to be extending its strong foothold across all Materials and Methods
Indianpopulationtypes.Arecentcross-sectionalanalysisof
representative samples of subjects from a South-Asia study Study population
and another for South Asians living in America showed a
Patients with T2D were recruited through physician re-
higher age-adjusted diabetes prevalence among Indians in
ferral at the outpatient department of the Fortis C-DOC
India (38%) than among Indians residing in the United
Center of Excellence for Diabetes, Metabolic Diseases and
States (24%).7 Another recent study in Maharashtra, India,
Endocrinology, Delhi. In accordance with the inclusion
to assess the risk factors for T2D among three different
criteria,thestudystaffrecruitedpatientsintheagerangeof
social and demographic class groups—affluent medical
25–70years,onstabledosesofmetforminforaperiodof3
students, rural subjects, and subjects from urban slums—
months,withglycosylatedhemoglobin(HbA1c)levels<9%,
demonstrated that the rural subjects, although the least
and low-density lipoprotein cholesterol (LDL-c) levels
sedentary and significantly more active than the medical
‡100mg/dL. The study excluded subjects on insulin ther-
students, were most centrally obese and at a higher risk for
apy, pioglitazone, insulin secretagogues, beta blockers or
T2D compared with the two other groups.8
steroids, or those suffering from diabetes for more than 10
Symptomsofthediseasearenotjustwidespreadbutarealso
years. Subjects with high uric acid levels (‡8mg/dL) and
occurringatayoungerage.Across-sectionalstudyofIndian
acceleratedhypertension(stage2hypertensionaccordingto
adolescents in rural Wardha (central India) found 14% of the Joint National Committee guidelines),26 uncontrolled
subjectswithimpairedfastingbloodglucose(FBG)values.9
hypothyroidism, acute infection, any debilitating disease,
Inaddition,theburdenofdysglycemiaisknowntotranslate
renal failure, or appreciable weight loss (>10%) in the
intoadditionaldiseaseburdens,suchashypertension,10car-
previous 6 months were also excluded from the study. Pa-
diovascular disease (CVD),11 metabolic syndrome,9 nonal-
tients were screened for any known food allergies, lipid-
coholicfattyliverdisease,12diabeticnephropathy,13diabetic
alteringmedications,orextraneousfactorsthatareknownto
retinopathy, liquefaction and syneresis of the vitreous14 pe-
affect glycemic or lipid parameters.
ripheralneuropathyleadingtofootulcerationandevenam-
putation,15 potential increased predisposition to hepatitis C
infection,16andco-morbiddepression.17,18Thecostofdeal- Ethics committee statement
ing with diabetes and its complications translates into a co- An independent review committee, ‘‘Ethics Committee
lossaleconomicburdenforthecountryanditspeople.19 forHumanResearch,’’approvedthestudyprotocolwiththe
Several factors are known to play a role in dictating the statement—TheEthicsCommitteeherebygivesanapproval
onset of prediabetes and the progression to T2D among toconductthestudyatFortisFlt.Lt.RajanDhallHospital,
Indians. However, the primary factor postulated for higher Vasant Kunj, New Delhi. Written informed consent form,
and earlier incidence in Indians versus other ethnicities has approvedbytheethicscommittee,wasobtainedfromallthe
come to be known as the ‘‘South Asian’’ or the ‘‘Asian study participants.
Indian’’ phenotype, which is characterized by higher waist The study was registered at clinicaltrials.gov with regis-
circumference, higher levels of total and visceral fat, hy- tration number NCT02027740.
perinsulinemia, insulin resistance, and, thus, a great pre-
dispositiontodiabetescomparedwithsomeotherethnicities
Study design
with comparable body mass index (BMI).5 With a genetic
predispositiontoinsulinresistanceandT2D,itisimperative Afree-livingpre–postinterventionstudydesignwasused
that Indians adopt lifestyle modifications to help delay toassesstheeffectofalmondsupplementationoveraperiod
prediabetesonsetandtomanagethediseasebetter.Nutrition of 24 weeks after a run-in control period of 3 weeks. The
isanimportantaspectofahealthylifestyle.Arecentreview studywasdesignedasapre–postinterventiontoensurethat
ofthenutrientintakeofAsianIndianandSouthAsiandiets all subjects received almond treatment. During the run-in
revealsalowintakeofmonounsaturatedfattyacid(MUFA), period (n=63), all subjects consumed standard diets for-
polyunsaturatedfattyacid(PUFA),andfiberandhighintake mulated according to the dietary guidelines for Asian Indi-
of saturated fats, trans-fatty acids, and carbohydrates.20 ans,appropriatetothediabetesstatusoftheindividual.The
The required change in Indian dietary patterns should be diet composition of the control diet was as follows: carbo-
inclusion of nutritious foods that are already part of Indian hydrates, 60%; protein, 15%; and fat, 25%. Subjects were
culture and can easily be accommodated into the everyday advised 45min of walking at least 5 days in a week and
100 GULATI, MISRA, AND PANDEY
Table 1. Changes in Outcome Variables After Run-In Period
Screening After 3 weeks
Variable Mean–SD Mean–SD Difference (95% CI) P-value
Total cholesterol (mg/dL) 201.4–31.4 202.3–31.4 0.9 (-6.8, 8.6) 0.802
Serum triglycerides (mg/dL) 182.5–87.5 195.3–112.1 12.8 (-9.1, 34.8) 0.212
Low-density lipoprotein (mg/dL) 133.9–19.7 131.1–21.4 -2.8 (-8.3, 2.6) 0.330
High-density lipoprotein (mg/dL) 41.7–9.3 42.1–8.9 0.4 (-1.1, 1.9) 0.635
Very low-density lipoprotein (mg/dL) 38.9–22.2 36.7–18.2 2.3 (-2.3, 6.9) 0.342
Fasting blood glucose (mg/dL) 133.9–31.3 131.9–29.2 -1.9 (-7.8, 3.8) 0.511
Glycosylated hemoglobin (%) 7.9–1.7 7.7–1.2 -0.2 (-0.5, 0.1) 0.128
SD,standarddeviation.
were asked to maintain the same level of physical activity Statistical methodology
throughout the study period. The subjects enrolled for the
Datawererecordedonpredesignedcasereportformsand
study were patients with T2D, already attending the outpa-
managedonExcelspreadsheets.Quantitativevariableswere
tient department frequently for treatment. These patients
summarizedasmean–standarddeviationormedian(range)
were previously given standardized diet and exercise
aspertheirdistribution(normal/non-normal).Apairedt-test
counseling repeatedly and were following such advice be-
wasusedtocomparepre-topostinterventiondifferencesin
fore recruitment in the study.
mean values. The Wilcoxon signed-rank test was used to
compare pre intervention (after the run-in period) to post-
Diet and compliance
intervention differences in median values. STATA 11.0
statistical software was used for data analyses.
After the run-in period, during the treatment phase, sub-
All the parameters were compared at the beginning and
jects received the almond diet and were advised on how to
attheendofrun-inperiod.Therewasnosignificantdifference
substitute 20% of total energy intake with whole raw al-
between before and after the run-in period in all the consid-
monds (unblanched kernels, with brown skin intact). In the
ered biochemical and anthropometric parameters (Table 1).
almond diet, almonds were substituted for some visible fat
(cookingoilandbutter)andaportionofcarbohydrates.The
Results
dietary composition of the almond diet was as follows:
carbohydrates, 55%; protein, 17%; and fat, 28%. Instruc- Study population
tionswereprovidedverballyandinwritingaccordingtothe
subject’s local language. Studystaffscreened190subjectsandenrolled63ofthese
Compliance to the study protocol was ensured through subjects on the basis of inclusion/exclusion criteria men-
compliance questionnaires, biweekly telephone calls with tioned above (Fig. 1). Five oftheenrolled subjects dropped
subjects, and cross-checks with spouses or family members out of the study during the run-in period: three due to re-
residing with the subjects. In addition, subjects were asked location and two due to personal reasons not related to the
to return empty almond packets on their hospital visits. study. A total of 58 subjects completed the run-in period.
Spouses and family members were also given a supply of Another threesubjects withdrew beforethetreatment phase
almonds for daily consumption to help ensure subject for personal reasons. A total of 55 subjects began the al-
compliance. Subject compliance to the protocol was found mond intervention, andatotal of 50subjects completed the
to be nearly 85%. study (Fig. 1), with two out of five dropouts lost to follow-
up and the remaining three lost to poor compliance. Of the
50completers,therewere27malesand23females,withan
Assessments
overallmeanageof45.8–9.3yearandameanbodyweight
Each subject’s right arm was used for blood pressure of 73.6–12.1kg, waist circumference of 99.4–9.2cm, and
measurement. According to standard protocol, the subject BMI of 28.7–4.5kg/m2 (Table 2).
was required to be in a relaxed sitting position.26 Assess-
ments for anthropometric, glycemia [FBG and glycosylated Anthropometry and blood pressure
hemoglobin (HbA1c)], and lipid parameters [total choles-
TherewasnosignificantchangeinbodyweightandBMI,but
terol (TC), serum triglycerides (TG), LDL-C, high-density
significant decreases in mean values of waist circumference
lipoprotein cholesterol (HDL-C), and very low-density li-
(P=0.03) and WHtR (P=0.05) were observed after almond
poprotein cholesterol (VLDL-C)] were carried out as de-
interventioncomparedwiththecontroldietgivenintherun-in
scribedpreviously.27BMIandwaist-to-heightratio(WHtR)
period(Table2).Bloodpressuremeasurementsdidnotchange
were calculated. HbA1c, lipoprotein(a) [Lp(a)], and high
significantlypostinterventioncomparedwiththecontroldiet.
sensitivity C-reactive protein (hs-CRP) levels were mea-
suredasdescribedpreviously.28–30Arterialstiffnessindices
Measures of glycemia
were assessed noninvasively by measuring carotid–femoral
pulse wave velocity with a SphygmoCor cuff (Atcor Med- FBG levels did not show a significant change over the
ica,Australia).Assessmentslistedabovewereconductedon course of the study (Table 2). Statistically significant im-
thefirstdayofenrollment,thelastdayoftherun-inperiod, provement was seen in levels of HbA1c (P=0.04) after al-
and the last day of the almond intervention period. mond intervention compared with the control diet (Table 2).
ALMOND INTERVENTION IN TYPE2DIABETESMELLITUS 101
FIG.1. {Investigation:anthropom-
etry, blood pressure, fasting blood
glucose (FBG), glycosylated hemo-
globin (HbA1c), total cholesterol
(TC),serumtriglycerides(TG),high-
densitylipoproteincholesterol(HDL-
C), low-density lipoprotein choles-
terol(LDL-C),lipoprotein(a)(LP(a)),
high sensitivity C-reactive protein
(hs-CRP), pulse wave velocity, diet,
and physical activity assessments.
{{Investigations:anthropometry,blood
pressure,FBG,lipids(TC,TG,HDL-
C,LDL-C).
Lipid parameters In addition to improved anthropometric measures, this
study demonstrated a statistically significant decrease in
Statistically significant improvements in levels of TC
HbA1c levels in subjects after almond supplementation
(P=0.002), TG (P=0.004), LDL-C (P=0.01), VLDL-C
compared with their levels on the control diet. HbA1C has
(P=0.007), and hs-CRP (P=0.01) were observed post- been validated for the diabetic Asian Indian population.34
intervention (Table 2). HDL-C did not change and Lp(a)
The HbA1c results from this study are comparable, maybe
demonstrated a trend toward reduction, although the de-
even better, to those obtained in other nut intervention
creasefailedtoattainstatisticalsignificance(Table2).Pulse
studies (Table 3).
wave velocity also demonstrated an improvement post-
HighHbA1Chasbeenfoundtobeassociatedwithgreater
intervention, however, the change was not statistically sig- waist circumference and higher serum triglycerides.35 Sub-
nificant (P>0.06).
jects in the current study demonstrated a concurrent and
significant decrease in HbA1C, waist circumference, and
Discussion
serum triglycerides (Table 2), thereby providing strong ev-
This study demonstrated that daily almond consumption idence in support of this association. It has also been clin-
at 20% of total energy intake for 24 weeks helped improve ically proven and scientifically accepted that any reduction
anthropometric,glycemic,andlipidparameterssignificantly in levels of HbA1C significantly decreases the risk of dia-
in Asian Indian subjects with T2D. betic complications.36 Although the incidence of diabetic
An intake of whole almonds adds protein, total dietary complications was not recorded in this study due to its
fiber, MUFAs, PUFAs, vitamin E, and potassium31 to the limited duration, the benefits of daily almond intake have
dietandhasbeenshownbyotherstoimprovethequalityof been shown by others to reduce risks of complications.33
dietwithoutincreasingenergyintake.23,32Thereisevidence The benefits of almonds on postprandial glucose regula-
fromotheralmondsupplementationstudiescollectivelythat tion have been clearly and consistently demonstrated in
almonds may have a greater impact on multiple cardiome- many studies.22,23,41,42 However, results from studies look-
tabolic health parameters in the same subjects.25,33 These ing at benefits resulting from chronic consumption have
multiple health benefits were observed in the current study beenmixed.AlthoughLietal.25demonstratedastatistically
as well. Waist circumference and WHtR decreased signifi- significant reduction in fasting glucose in 58-year-old Tai-
cantlyafteralmondsupplementation(Table2)andmaywell wanese subjects with T2D on a 60g daily dose of almonds
explain the benefits on glycemia and lipid parameters for 4 weeks, the current study failed to demonstrate a sta-
observed in the subjects. tistically significant difference on fasting glucose levels.
value 192071031*05*002*004*011*301005*310411041*011*221530402061 bloodpulse
(50)n= Difference(95%CI)P 0.7(1.7,0.4)0.--0.3(0.6,0.03)0.--1.6(3.2,0.1)0.---0.009(0.02,0.002)0.--13.9(22.3,5.7)0.---—0.8.2(14.7,1.7)0.---0.9(2.7,0.8)0.--—0.—0.3.5(11.9,4.9)0.--0.3(0.6,0.01)0.---—0.—0.1.2(5.1,2.7)0.--0.8(3.1,1.5)0.--—0. haveaneffectonthem. oteincholesterol;FBG,fastingdiastolicbloodpressure;PWV,
utcomeVariablesPre-andPostIntervention #Allcompliant DifferencePreinterventionPostintervention(95%CI)valuemeanSDmeanSDP–– 8(1.7,0.1)0.07173.612.472.912.2-––3(0.6,0.06)0.02228.74.428.54.7-––3(2.5,0.09)0.0499.49.297.810.4--––7(0.02,0.001)0.050.620.070.610.08-––1(17.7,4.4)0.001201.332.1187.422.7--––—0.002170.5(59,499)149.5(72,499)5(11.7,1.3)0.021129.722.5121.518.5--––7(2.1,0.6)0.30141.68.940.79.8-––—0.00534.1(11.8,103)28.5(14.4,99.8)—0.20121.8(9.38,122)19.8(9.38,111)8(9.4,3.9)0.403133.531.4129.934.7-––3(0.5,0.01)0.0407.71.27.31.1--––—0.0113.3(0.3,4.9)2.6(0.2,13.6)—0.4039.39(1.3,83.2)8.75(1.3,157)9(4.1,2.1)0.501122.215.812110.4-––8(3.1,1.5)0.52378.26.677.45.9-––—0.0338.1(4.2,19)7.8(4.5,16.6) arriedforwardaspostinterventionvaluesassumingthatinterventiondidnot DL-C,high-densitylipoproteincholesterol;VLDL-C,verylow-densitylipoprn;U.microalbumin,urinemicroalbumin;SBP,systolicbloodpressure;DBP,
sinO 63)n= 0.-0.-1.-0.00-11.- 6.-0.- 2.-0.- 0.-0.- werec erol;Heprotei
TableChange2. Allenrolled( #PreinterventionPostinterventionmeanSDmeanSDOutcomevariable–– a74.912.474.111.9Weight(Kg)––a2)28.94.428.64.5BMI(Kg/m––aWaistcircumference(cm)100.19.498.710.4––a0.620.070.610.08Waist–heightratio––aTotalcholesterol(mg/dL)202.331.4191.225.1––b195.3(59,499)175.4(72,499)S.Triglycerides(mg/dL)aLDL-C(mg/dL)131.121.4124.618.9––a42.18.941.39.7HDL-C(mg/dL)––bVLDL-C(mg/dL)34.4(11.8,99.8)29.8(14.4,99.8)b(mg/dL)21.4(9.4,122)19.8(9.4,111)Lipoprotein(a)aFBG(mg/dL)131.929.2129.231.8––aHbA1C(%)7.71.27.41.1––bhs-CRP(mg/L)2.9(0.4,34.9)2.6(0.2,13.6)b9.4(1.3,83.4)9.0(1.3,157)U.microalbumin(mg/L)–aSBP(mmHg)122.715.7121.711.6––aDBP(mmHg)78.26.677.66.1––bPWV(m/s)8.1(4.2,19)7.9(4.5,17.0) atValuesarepresentedasmeanSD,paired-test.–bValuesarepresentedasmedian(range),Wilcoxonsignranktest.p*0.05:statisticallysignificant.<#Subjectswhowerenotavailablepostintervention,preinterventionvalues—Differencecouldnotbecalculated.S.triglycerides,serumtriglycerides;LDL-C,low-densitylipoproteincholestglucose;HbA1C,glycosylatedhemoglobin;hs-CRP,highlysensitiveC-reactivwavevelocity.
102
ALMOND INTERVENTION IN TYPE2DIABETESMELLITUS 103
Table 3. Comparison of HbA1C Value After Intervention with Tree Nuts in Selected Studies
Intervention
Subject type; Subject Nut treatment: duration Baseline End of intervention
Study completers (n) age (year) amount (g) (month) HbA1c (%) HbA1c (%) P value
Tapsell et al.37 T2Da; 18 54–8.7 Walnuts: 30 6 7.3–1.2 7.1–1.5 0.023
Jenkins et al.38 T2Da; 40 63 Mixed nuts: 3 7.1–0.2 6.9–0.2 0.001
50–100
Cohen et al.39 T2Da; 6b 66.0–3.3 Almonds: 28 3 7.1–0.2 6.8–0.3 0.045
Gulati et al.40 MetSc; 30 41.6–8.4 Pistachios 6 5.9–0.4 5.7–0.3 0.301
aT2Dreferstotype2diabetessubjecttype.
bPilotstudy.
cMetSreferstosubjectswithmetabolicsyndromeaspermodifiedInternationalDiabetesFederationdefinition.
With no difference observed in fasting glucose and in the pre–post design of the study using run-in as control period
absence of fasting insulin measures, it is difficult to postu- reducesdatavariability,therebyincreasingthecredibilityof
latethepotentialmechanismofactioninvolvedintheother the results obtained. The role of almonds in insulin man-
observed benefits. agement clearly remained elusive and needs further explo-
Similar results for fasting glucose levels have been ob- ration.
served in several mixed-nuts studies with almond intake. In terms of its strength, this is the first study ever dem-
Despite reporting a significant improvement in HbA1c, in- onstrating health benefits of almond consumption in free-
sulin resistance, insulin sensitivity, or insulin levels, these living Asian Indians with T2D, despite their unique Asian
studies have failed to show a change in FBG.38,43,44 These Indian phenotype and their predisposition toward the dis-
results suggest that the preferred mechanism of action of ease. This study provides scientific proof of the value of
almonds behind long-term glycemic control might be almondconsumptiontoapopulationthatalreadybelievesin
through a pivotal role in insulin management rather than in the goodness of almonds.
reduction of glucose absorption or increased clearance.
The relationship between fasting blood lipid levels, par-
Acknowledgments
ticularly levels of LDL-C and TC, and the risk of CHD is
wellestablishedinthescientificliterature.45–47Specifically, The authors are thankful to all the participants of the
for every 1% reduction in LDL-C, there is a corresponding study for their cooperation. This study was fully supported
1%–2% decrease in the risk of CHD.45,48 Results from the by a grant from Almond Board of California, USA.
current study demonstrated a statistically significant de-
crease in levels of TC, LDL-C, and VLDL-C after almond Author Contributions
supplementation in study subjects compared with intake of
the control diet. Comparable results have been observed in S.G. researched data, conducted the study, wrote the ar-
multiplestudiesconductedusingsimilaralmondintake.49–54 ticle, A.M. conceived the study idea, supervised the study,
As observed in other almond consumption studies, HDL-C wrote the article, reviewed/edited the article, and R.M.P.
didnotchangesignificantlyafteralmondconsumptionwhen performed the statistical analysis and reviewed the article.
compared with the control diet.52,55–57 This might also be
indicative of the preferred mechanism of action for al- Author Disclosure Statement
monds, working primarily on the cluster of lower density
lipoproteins. No competing financial interests exist.
In addition to improved lipid levels, the subjects dem-
onstrated significant improvement inhs-CRP levels. Higher References
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The current study had a few obvious limitations, partic-
3. InternationalDiabetesFederation.TheIDFDiabetesAtlas,
ularlytheabsenceofinsulinmeasures,followedbyashorter
7th Edition 2015. Accessed at www.oedg.org/pdf/1606_
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