garlic supplementation for hyperlipidemia soto, tanggol, teo, torio, torregrosa, tuddao, tumangday,...
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GARLIC SUPPLEMENTATION FOR HYPERLIPIDEMIA
Soto, Tanggol, Teo, Torio, Torregrosa, Tuddao, Tumangday, Valenzuela, Valerio, Vidal, Villanueva, Ampil
NORMAL VALUES:
Total cholesterol:< 200 mg / dL (for >19 y/o)
Triglycerides:< 150 mg / dL
HDL-c:40 – 60 mg / dL
LDL-c:< 100 mg / dL
$
(+)
(-)
“Does garlic
supplementation have a
lipid lowering effect in
hyperlipidemic patients?”
P = Hyperlipidemic PatientsI = Garlic SupplementationC = PlaceboO = Lipid ProfileM = RCTs
METHODOLOGY
CRITERIA FOR CONSIDERING STUDIES
• Randomized Controlled Trial- May or may not involve crossover period
• May be unblinded, single-blinded or double-blinded
• Published or Unpublished
• English Articles
TYPE OF STUDY
• Adults (19 years old above)• With mild, moderate or severe
hypercholesterolemia• No comorbid illnesses• No other pathological clinical chemistries• Not taking any other medications• Not taking any substantial amount of
garlic in the diet
TYPES OF PARTICIPANTS
• Garlic Supplementation– Any form (tablet, capsule, aged garlic
extract or oil for) versus placebo – May have minor ingredients that are not
known to have an effect on the outcome– May or may not be taken with meals– Any dose– At least four weeks of intervention
TYPES OF INTERVENTIONS
• Total Cholesterol
• Low Density Lipoprotein Cholesterol (LDL-C)
• High Density Lipoprotein Cholesterol (HDL-C)
• Triglycerides
TYPES OF OUTCOME MEASURES
• Systematic online article search via PubMed– MESH terms “garlic AND dyslipidemias”– LIMITS: humans, RCTs, English, All adult
19+
SEARCH METHODS FOR IDENTIFICATION OF STUDIES
LIMITS: RCT, Humans, all adults > 19 y/o, English only
LIMITS: RCT, Humans, all adults > 19 y/o, English only
24RCTs 24RCTs
Studies that met the inclusion criteria
(n=14)
Studies that met the inclusion criteria
(n=14)
3 Full-text RCTs cannot be retrieved3 Full-text RCTs cannot be retrieved
11 Full-text RCTs included
11 Full-text RCTs included
Excluded studies (n=10)Excluded studies (n=10)
“Garlic” [MESH] AND “dyslipidemias” [MESH] (n=111) “Garlic” [MESH] AND “dyslipidemias” [MESH] (n=111)
• Cross-referencing of all appraised articles– 2 articles included
• Free text search via Yahoo and Google search engine– Various combinations of the search terms
(cholesterol-lowering effects, garlic, allicin, allium sativum, hyperlipidemia, and hypercholesterolemia)
– 1 article included
SEARCH METHODS FOR IDENTIFICATION OF STUDIES
SEARCH METHODS FOR IDENTIFICATION OF STUDIES
• Other Databases—Cochrane —Medscapepharmacist—HighWire Press (a
Division of the Stanford University Library)
—Herdin—DOH-OPAC—UP-PGH College of
Medicine OPAC
—UPD-College of Science OPAC
—UST-OPAC—Kansas University
Libraries OPAC —SLCM-WHQM Medical
Library OVID Program and Journal Collection
SEARCH METHODS FOR IDENTIFICATION OF STUDIES
• Hand Searching– RBD-SLMC– Department of Nutrition-SLMC– Manufacturers of locally available garlic
supplements – Cardiologists at St. Luke’s Medical Arts
Building and Cathedral Heights Building Complex (CHBC) were also contacted through telephone and/or visits to their clinics
• Assessed using the EBM approach
METHODOLOGICAL QUALITY
Rating Description
A All of the primary and secondary criteria was met
B At least one secondary criteria not met
C At least one primary criteria was not met but dropouts <20%
D At least one primary criteria was not met but dropouts >20%
TOTAL NUMBER OF INCLUDED STUDIES
FOURTEEN
• All double-blinded RCTs (n=14)– 4 studies with crossover
• Population– Hyperlipidemic male and female adults – No other comorbidities/abnormal serum
parameters aside from hypercholeserolemia– Not taking any garlic supplementation, any
other medications– No substantial amount of garlic in their diet
DESCRIPTION OF STUDIES
• Thirteen of the fourteen studies were homogenous at baseline, the remaining study adjusted using analysis of covariance
• Thirteen randomized hyperlipidemic subjects with garlic versus placebo or no intervention, the remaining article
randomized hyperlipidemic subjects with garlic versus anethum graveolens or placebo
DESCRIPTION OF STUDIES
• Intervention– Garlic supplementation• Form–Capsule or tablet
• Dose–Range: 400mg/day-7,200mg
• Duration–Range: 6 weeks-5 months
DESCRIPTION OF STUDIES
Description of StudiesRating Description No. of Studies
A All of the primary and secondary criteria was met 3
B At least one secondary criteria not met 2
C At least one primary criteria was not met but dropouts <20%
9
D At least one primary criteria was not met but dropouts >20%
0
• Mean change from baseline– Total Cholesterol, LDL-Cholesterol, HDL-
Cholesterol and Triglycerides
• Mean percent change– Total Cholesterol, LDL-Cholesterol, HDL-
Cholesterol and Triglycerides
MEASUREMENTS OF TREATMENT EFFECT
SUBGROUP ANALYSIS
• Diet– No change in diet (n=7)– Diet Advice (n=2)– Strict Dietary Regimen (n=5)
• Sex– All males (n=3)– Males and Females (n=11)
• Crossover Trials– The group used the lipid parameters
given in the study prior to the crossover period
• One study (Steiner, et al.) did not show the exact values , the group estimated the values through the given graphs
UNIT OF ANALYSIS ISSUES
• Random Effects Model
• Fixed Effects Model
DATA SYNTHESIS
RESULTS AND DISCUSSION
14 INCLUDED STUDIES
1 excluded from statistical analysis
MEAN CHANGE(N = 592-625 )
MEAN PERCENT CHANGE(N = 183 )
SEX DIET
MIXED (M& F)
MALES only
NO dietary change
Dietary advice
Diet regimen
SEX DIET
MIXED (M&F)
MALES only
NO dietary change
Dietary advice
Diet regimen
Total cholesterol, LDL-C, HDL-C, Triglyceride
RESULTS
STANDARD DEVIATION
• Only 3 studies showed the SD for mean change and/or mean percent from baseline:1. Isaacsohn et al.2. Kojuri et al.3. Superko et al.
• 10/13: no SD cited SD values were imputed
NOT INCLUDED IN THE STATISTICAL ANALYSIS
• Berthold et al. No significant effect
• Mader et al. and Vorberg and Schneider Significantly decreased total cholesterol
and triglyceride levels
• Silady et al. no significant differences bet. the 2
groups
TOTAL CHOLESTEROL (TC)
Fig.2 Comparison of Mean Change from Baseline of Total Cholesterol Levels
TOTAL CHOLESTEROL (TC)
Fig.3 Comparison of Mean Percent Change from Baseline of Total Cholesterol Levels
LDL-C
Fig.4 Comparison of Mean Change from Baseline of LDL-C Levels
LDL-C
Fig.5 Comparison of Mean Percent Change from Baseline of LDL-C Levels
HDL-C
Fig.6 Comparison of Mean Change from Baseline of HDL-C Levels
HDL-C
Fig.7 Comparison of Mean Percent Change from Baseline of HDL-C Levels
TRIGLYCERIDE (TG)
Fig.8 Comparison of Mean Change from Baseline of Triglyceride Levels
Fig.9 Comparison of Mean Percent Change from Baseline of Triglyceride Levels
TRIGLYCERIDE (TG)
SUMMARY OF RESULTS• Mean change from baseline of TC and LDL-C
Favored the garlic treatment group Significantly decreased levels
• Mean change from baseline of HDL-C and TG Favoured the garlic treatment group, but not significant
• Mean percent of all lipid parameters Not significant small number of participants
SUBGROUP ANALYSES
SEX
Males OnlyMixed (Males and Females)
SEX: MALES ONLY
Total Cholesterol
SEX: MALES ONLY
LDL-C Levels
SEX: MALES ONLY
HDL-C Levels
SEX: MALES ONLY
Comparison of Mean Change from Baseline of Triglyceride Levels
SEX: MALES ONLY
• Garlic increased triglycerides significantly– (WMD -5.80mg/dL; 95% CI -5.86 to -5.74)
• Exact mechanism is still unclear.• Libby et al. (2008)– the impact of triglycerides in the
development of CHD also remains unclear• imprecision in triglyceride measurements and
the complex interactions between triglycerides and other lipid parameters
Total Cholesterol Levels
SEX: MIXED (MALES AND FEMALES)
HDL-C Levels
SEX: MIXED (MALES AND FEMALES)
SEX: MIXED (MALES AND FEMALES)
Triglyceride Levels
SEX: MIXED (MALES AND FEMALES)
LDL-C Levels
SEX: MIXED (MALES AND FEMALES)
• Decreased LDL-C but not significantly – (WMD 6.86 mg/dL; 95% CI -1.54 to 15.26)
• May be due to presence of confounders gender of the participants
• Protein phosphorylation by AMP-dependent kinase (AMPK) • inhibition of hydroxy-methyl-CoA reductase
(HMGR) and acetyl-CoA-carboxylase
DIET
No Dietary ChangeDietary Advice
Specific Diet Regimen
NO DIETARY CHANGE
Total Cholesterol Levels
NO DIETARY CHANGE
LDL-C Levels
NO DIETARY CHANGE
HDL-C Levels
NO DIETARY CHANGE
Triglyceride Levels
• Defined as low fat (monounsaturated and polyunsaturated) and low carbohydrate diet
• with subsequent reduction in alcohol intake
DIETARY ADVICE
DIETARY ADVICE
Total Cholesterol Levels
DIETARY ADVICE
Triglyceride Levels
DIETARY ADVICE
Comparison of Mean Change from Baseline of LDL-C Levels
DIETARY ADVICE
• Decreased LDL-C but not significant(WMD 11.84 mg/dL; 95% CI -2.45 to 26.13)
• May be attributed to timing of implementation of the dietary advice– done before randomization occurred– diet may have already induced an effect
on the participants’ lipid parameters– effect of garlic treatment underestimated.
DIETARY ADVICE
Comparison of Mean Change from Baseline of HDL-C Levels
• Significantly decreased HDL-C level (WMD 3.31 mg/dL; 95% CI 0.88 to 5.74)
• May be due to compliance– Kannar et al. (2000): compliance with
dietary advice is LOW• May also be due to decreased alcohol
intake– Alcohol is thought to increase the HDL-C
levels
DIETARY ADVICE
SPECIFIC DIETARY REGIMEN
Comparison of Mean Change from Baseline of Triglycerides Levels
SPECIFIC DIETARY REGIMEN
Total Cholesterol Levels
SPECIFIC DIETARY REGIMEN
• Garlic decreased total cholesterol– but not significantly– (WMD 13.21 mg/dL; 95% CI -2.01 to 28.43)
• May be due to also due to timing of diet supplementation
SPECIFIC DIETARY REGIMEN
Comparison of Mean Change from Baseline of LDL-C Levels
SPECIFIC DIETARY REGIMEN
• Garlic decreased LDL-C– but not significantly – (WMD 10.55 mg/dL; 95% CI -5.51 to 26.62)
• May be due to also due to timing of diet supplementation
SPECIFIC DIETARY REGIMEN
Comparison of Mean Change from Baseline of HDL-C Levels
SPECIFIC DIETARY REGIMEN
• Garlic increased HDL-C significantly– (WMD -5.80 mg/dL; 95% CI -5.86 to -5.74)
• May be due to compliance w/ diet– compliance was monitored through a
food diary and calculation of 24 hour nutrient intake
– studies under this subgroup fully met the dietary goals prescribed to the participants
CONCLUSION • Garlic treatment significantly reduces
the total cholesterol and LDL-C levels among hyperlipidemic patients.
• There is no sufficient evidence that garlic affects the HDL-C and triglyceride levels.
CONCLUSION
• Garlic supplementation markedly improves the serum lipid levels of hyperlipidemic men.
• The hypolipidemic effect is augmented by an approved dietary regimen.
IMPLICATION FOR PRACTICE• Recommend the use of garlic as a
supplement to lower the lipid levels among hyperlipidemic patients.
• Garlic should not be used as the primary lipid-lowering medication.
IMPLICATION FOR RESEARCH
• More studies involving a larger number of participants is recommended.
• More well designed studies should be included.
• Normolipidemic patients may also be included in the future to determine the applicability of effects of garlic supplementation to these patients.
IMPLICATION FOR RESEARCH
• A subgroup analysis may also be done on dose, length of intervention, and the severity of hyperlipidemia to determine the most appropriate dose and duration of garlic supplementation for certain populations.