garlic supplementation for hyperlipidemia

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• Published or Unpublished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

24RCTs

Studies that met the inclusion criteria

(n=14)

3 Full-text RCTs cannot be retrieved

11 Full-text RCTs included

Excluded studies (n=10)

“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.