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  • Grade Chart
  • Saturated Fat (DLM-SF) Guideline (2021-23)
    • DLM-SF: Acronyms and Abbreviations (2023)
    • DLM-SF: Executive Summary of Recommendations (2023)
    • DLM-SF: Guideline Introduction (2023)
      • DLM-SF: Guideline Overview (2023)
      • DLM-SF: Scope of Guideline (2023)
      • DLM-SF: Statement of Intent (2023)
      • DLM-SF: Guideline Identifying Information (2023)
    • DLM-SF: Methodology (2023)
      • DLM-SF: Systematic Review and Guideline Methods (2023)
      • DLM-SF: Guideline References (2023)
    • DLM-SF: Recommendations and Supporting Evidence (2023)
    • DLM-SF: Benefits and Risks/Harms of Implementation (2023)
    • DLM-SF: Dissemination and Implementation of the Guideline (2023)
  • Saturated Fat (DLM-SF) Systematic Review (2018-2021)
    • DLM-SF: Amount of Saturated Fat (2018-21)
      • DLM-SF: Amount of Saturated Fat Intake Summary Table (2021)
      • DLM-SF: Endothelial Function (2021)
      • DLM-SF: Inflammation (2021)
      • DLM-SF: Blood Lipids (2021)
      • DLM-SF: Cardiovascular Events (2021)
      • DLM-SF: Cardiovascular Disease Mortality (2021)
      • DLM:-SF Coronary Heart Disease Events (2021)
      • DLM-SF: Coronary Heart Disease Mortality (2021)
      • DLM-SF: Stroke (2021)
      • DLM-SF: All-Cause Mortality (2021)
    • DLM-SF: Replacement of Saturated Fat (2018-21)
      • DLM-SF: Reduction and Replacement of Saturated Fat Intake and Blood Lipids Summary Table (2021)
      • DLM-SF: Replacement of Saturated Fat (2018-21)
    • DLM-SF: Sources of Saturated Fat (2018-21)
      • DLM-SF: Sources of Satured Fat Summary Tables (2021)
      • DLM-SF: Meat (2021)
      • DLM-SF: Cheese (2021)
      • DLM-SF: Milk (2021)
      • DLM-SF: Yogurt (2021)
      • DLM-SF: Butter (2021)
      • DLM-SF: Dairy Compared to Non-Dairy (2021)
      • DLM-SF: Dairy Comparisons (2021)

  • Intervention
    What does the evidence indicate is the relationship between serum homocysteine and the incidence of CHD?
    • Conclusion

      A high level of serum homocysteine, independent of other cardiac risk factors, has been associated with increased risk for coronary heart disease. Conversely, low homocysteine levels have been associated with reduced risk.

    • Grade: II
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    What effect does folic acid supplementation (with or without additional B vitamin supplementation) have on risk of CVD among persons with or without pre-existing vascular disease?
    • Conclusion

      The ADA Disorders of Lipid Metabolism workgroup concurs with the following statement and grade from the USDA Nutrition Evidence Library (NEL):

      Strong evidence demonstrates that folic acid supplementation with or without additional B vitamins in adult men and women with pre-existing vascular disease, does not appear to reduce risk of cardiovascular disease, and may increase risk slightly.



       

    • Grade: I
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Evidence Summary: What effect does folic acid supplementation (with or without additional B vitamin supplementation) have on risk of CVD among persons with or without pre-existing vascular disease?
      • Detail
      • Quality Rating Summary
        For a summary of the Quality Rating results, click here.
      • Worksheets
        • Albert CM, Cook NR, Gaziano JM, Zaharris E, MacFadyen J, Danielson E, Buring JE, Manson JE. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: A randomized trial. JAMA. 2008; 299: 2,027-2,036.
        • Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases: A meta-analysis of randomized controlled trials. JAMA 2006 Dec 13; 296 (22): 2,720-2,726. Erratum in: JAMA. 2007 Mar 7; 297 (9): 952. 
        • Bønaa KH, Njølstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K; NORVIT Trial Investigators. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006; 354 (15): 1,578-1,588
        • Ebbing M, Bleie O, Ueland PM, Nordrehaug JE, Nilsen DW, Vollset SE, Refsum H, Pedersen EK, Nygård O. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: A randomized controlled trial. JAMA. 2008; 300 (7): 795-804.
        • Ray JG, Kearon C, Yi Q, Sheridan P, Lonn E; Heart Outcomes Prevention Evaluation 2 (HOPE-2) Investigators. Homocysteine-lowering therapy and risk for venous thromboembolism: A randomized trial. Ann Intern Med. 2007; 146 (11): 761-767.
    What effect does folic acid supplementation (with or without additional B vitamin supplementation) have on risk of stroke among persons with or without pre-existing vascular disease?
    • Conclusion

      The ADA Disorders of Lipid Metabolism workgroup concurs with the following statement and grade from the USDA Nutrition Evidence Library (NEL):

      Evidence that folic acid supplementation might prevent stroke is limited due to inconsistency, with the most recent meta-analysis documenting no benefit.

       

       

    • Grade: III
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
    • Evidence Summary: What effect does folic acid supplementation (with or without additional B vitamin supplementation) have on risk of stroke among persons with or without pre-existing vascular disease?
      • Detail
      • Quality Rating Summary
        For a summary of the Quality Rating results, click here.
      • Worksheets
        • Al-Delaimy WK, Rexrode KM, Hu FB, Albert CM, Stampfer MJ, Willett WC, Manson JE. Folate intake and risk of stroke among women. Stroke. 2004; 35(6):1259-63. 
        • Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases: A meta-analysis of randomized controlled trials. JAMA 2006 Dec 13; 296 (22): 2,720-2,726. Erratum in: JAMA. 2007 Mar 7; 297 (9): 952. 
        • Miller ER 3rd, Juraschek S, Pastor-Barriuso R, Bazzano LA, Appel LJ, Guallar E. Meta-analysis of folic acid supplementation trials on risk of cardiovascular disease and risk interaction with baseline homocysteine levels. Am J Cardiol 2010. Abstracted prior to publication.
        • Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E; Heart Outcomes Prevention Evaluation 2 Investigators. Homocysteine-lowering therapy and stroke risk, severity, and disability: Additional findings from the HOPE 2 trial. Stroke. 2009; 40 (4): 1,365-1,372.
        • Virtanen JK, Voutilainen S, Happonen P, Alfthan G, Kaikkonen J, Mursu J, Rissanen TH, Kaplan GA, Korhonen MJ, Sivenius J, Salonen JT. Serum homocysteine, folate and risk of stroke: Kuopio Ischaemic Heart Disease Risk Factor Study. Eur J Cardiovasc Prev Rehabil 2005; 12(4):369-375.
        • Wang X, Qin X, Demirtas H, Li J, Mao G, Huo Y, Sun N, Liu L, Xu X. Efficacy of folic acid supplementation in stroke prevention: A meta-analysis. Lancet. 2007; 369 (9,576): 1,876-1,882.
        • Weng LC, Yeh WT, Bai CH, Chen HJ, Chuang SY, Chang HY, Lin BF, Chen KJ, Pan WH. Is ischemic stroke risk related to folate status or other nutrients correlated with folate intake.  Stroke. 2008. 39:3152-8.
        • Yang LK, Wong KC, Wu MY, Liao SL, Kuo CS, Huang RF. Correlations between folate, B12, homocysteine levels, and radiological markers of neuropathology in elderly post-stroke patients. J Am Coll Nutr. 2007 Jun;26(3):272-8
    Does supplemental folate and/or Vitamins B6 and B12 reduce homocysteine levels and subsequently reduce coronary events?
    • Conclusion

      Supplemental folate (0.5-2.5 mg) given alone or in combination with B6 (10-25 mg) and B12 (0.4 mg) reduce homocysteine levels by 17-34% but did not reduced the risk for coronary events after 6 months to 2 years in stable CAD patients, post-stroke patients or post-angioplasty patients that had normal baseline homocysteine and total cholesterol concentrations.

    • Grade: II
      • Grade I means there is Good/Strong evidence supporting the statement;
      • Grade II is Fair;
      • Grade III is Limited/Weak;
      • Grade IV is Expert Opinion Only;
      • Grade V is Not Assignable.
      • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
      • Moderate (B) means we are moderately confident in the effect estimate;
      • Low (C) means our confidence in the effect estimate is limited;
      • Very Low (D) means we have very little confidence in the effect estimate.
      • Ungraded means a grade is not assignable.
 
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