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What Do Homocysteine Test Results Tell Us?

Why This Was Updated?

Our specialists regularly review advancements in health and wellness, ensuring our articles are updated with the newest information as it becomes accessible.
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Homocysteine is an amino acid derived from the metabolism of methionine, an essential amino acid obtained from the diet. In the body, homocysteine can be converted into other amino acids or recycled back to methionine with the help of certain B vitamins. Elevated levels of homocysteine in the blood are associated with an increased risk of cardiovascular and neurological diseases. Maintaining optimal homocysteine levels is crucial for overall health, as high levels can lead to inflammation and damage to blood vessels.

Elevated homocysteine levels can indicate potential vitamin deficiencies or genetic factors that impair the body's ability to metabolize this amino acid properly. By identifying and addressing the root causes of elevated homocysteine, functional medicine practitioners can develop targeted interventions, such as personalized nutrition plans and supplementation strategies, that optimize homocysteine levels and reduce the risk of related health issues. Understanding the importance of homocysteine in functional medicine allows healthcare providers to implement proactive measures, promoting overall wellness and preventing the onset of serious health conditions.

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The Biochemical Role of Homocysteine

Homocysteine is a sulfur-containing amino acid produced through the metabolism of methionine, an essential amino acid obtained from the diet. Homocysteine is involved in methylation, the transfer of a methyl group from one molecule to another. Methylation reactions are involved in numerous biological processes, including gene expression, protein function, neurotransmitter synthesis, and detoxification. (32, 43)

The body tightly regulates the homocysteine levels in the body through the methionine-homocysteine cycle. Methionine is converted to S-adenosylmethionine (SAMe). SAMe, often called the body's universal methyl donor, donates its methyl group to various substrates and is converted to S-adenosylhomocysteine (SAH). SAH is then converted to homocysteine. (31)Β 

Homocysteine has two possible fates. It can be remethylated to methionine in a reaction that requires vitamin B12 and folate. Alternatively, it can enter the transsulfuration pathway to be converted to cysteine, a reaction that requires vitamin B6 and leads to the synthesis of glutathione. (32, 43)Β 

A balance between these pathways is essential for maintaining proper levels of methionine and homocysteine in the body. Disruptions in this cycle can lead to elevated homocysteine levels (hyperhomocysteinemia). High homocysteine levels are associated with an increased risk for cardiovascular, cerebrovascular, and thromboembolic diseases. Therefore, understanding how homocysteine is produced in the body and its role in the methylation cycle is essential for maintaining proper biochemical balance and overall health. (32)Β 

Source: ResearchGate

Why Test for Homocysteine?

Serum homocysteine can be measured with a simple blood test. It can also be helpful to measure homocysteine in the context of a more comprehensive methylation panel, which measures other analytes involved in the methylation cycle and can help identify nutritional deficiencies contributing to abnormal homocysteine levels.Β 

Homocysteine increases as we age. Studies have found elevated homocysteine levels in almost 30% of people older than 65 and more than 40% in people 80 and older. This is relevant to aging and disease prevention because hyperhomocysteinemia has long been established as a risk factor for ischemic heart disease, heart attack, sudden cardiac death, premature coronary artery disease, carotid artery stenosis (narrowing), blot clots, stroke, and peripheral vascular disease. Newer studies have also identified high homocysteine as an independent risk factor for dementia and cognitive impairment; homocysteine levels higher than 15 Β΅mol/L are associated with nearly double the prevalence of dementia. A 2017 study showed that patients with Parkinson's disease and cognitive dysfunction were more likely to have higher homocysteine levels.Β 

By measuring homocysteine levels, healthcare providers can assess your risk factors, identify possible vitamin deficiencies, and develop targeted interventions to optimize your levels. Addressing elevated homocysteine through dietary changes, supplements, and lifestyle modifications may reduce your risk of developing chronic health conditions. Regular testing allows for proactive health management, aiding in the prevention of serious medical conditions and promoting overall well-being.

Understanding Homocysteine Test Results

Normal and optimal homocysteine levels should be less than 10 Β΅mol/L. Levels between 10-15 Β΅mol/L are considered borderline. (15) Hyperhomocysteinemia is diagnosed with a serum homocysteine level greater than 15 Β΅mol/L. There are three classifications of hyperhomocysteinemia, as follows (32):Β 

  • Moderate: 16-30 Β΅mol/L
  • Intermediate: 31-100 Β΅mol/L
  • Severe: > 100 Β΅mol/L

In a study of over 57,000 American adults, 1.8% of individuals had intermediate or severe hyperhomocysteinemia. This same study found that patients with homocysteine greater than 30 Β΅mol/L were more likely to have hypothyroidism, kidney disease, and a prescription for an antidepressant, opioid, steroid, or thyroid hormone medication. (29)Β 

Causes of Elevated Homocysteine Levels

Elevated homocysteine levels do not necessarily mean you have a cardiovascular or neurological disease. Factors that can impair homocysteine metabolism and contribute to elevated levels include (16, 43):

  • Comorbid medical conditions: cancer, diabetes, kidney disease, thyroid dysfunction, homocystinuriaΒ 
  • Folate, vitamin B6, and vitamin B12 deficiencies
  • Dietary factors: excess consumption of alcohol, coffee, and methionine-rich foods
  • Genetic variations of the cystathionine Ξ²-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR) genes
  • Older age
  • Male sex
  • Sedentary lifestyle
  • Smoking

Health Implications of High Homocysteine

Elevated levels of homocysteine damage the inner endothelial lining of blood vessels, promoting inflammation and oxidative stress in the vasculature. This increases the risk of atherosclerosis, a thickening and hardening of arteries caused by plaque buildup, and blood clots. Atherosclerosis is a primary cause of cardiovascular disease, including coronary artery disease (CAD), heart attack, heart failure, and stroke. (32)Β 

Studies show that nutritional interventions with homocysteine-lowering B vitamins slow the rate of brain atrophy in elderly with mild cognitive impairment. It is unclear if homocysteine directly causes brain atrophy or if these findings are related to vitamin deficiencies. Nevertheless, the evidence does support that homocysteine is neurotoxic and decreases blood perfusion to the brain. Elevated levels are associated with neurodegeneration progression, as observed in diseases like Alzheimer's disease. (32)Β 

There is also a correlation between high homocysteine levels and depression. In a study including over 900 middle-aged men, researchers found that individuals in the upper tertile for homocysteine levels had more than a two-fold increased risk for depression than those in the lowest tertile. Another study found that individuals with homocysteine levels greater than 12 Β΅mol/L had significantly lower SAMe, mood-enhancing neurotransmitters, and red blood cell folate levels.Β 

Osteoporosis and hip fracture are correlated with elevated homocysteine. Not only does homocysteine promote oxidative stress, but it also interferes with collagen cross-linking, altering the bone matrix composition and increasing bone fragility. (3)Β 

Strategies to Lower Homocysteine

If you have been diagnosed with hyperhomocysteinemia, the fortunate news is that there are many natural ways to reduce homocysteine levels. Dietary factors that cause high homocysteine may be addressed through dietary modifications and supplementation. However, it's important to remember that increasing your intake of vitamins does not wholly reduce the risk of chronic diseases. In addition to the therapeutic interventions discussed below, you can reduce your risk of heart and neurological disorders by quitting smoking, managing blood pressure and diabetes, getting adequate sleep, and exercising regularly.Β 

Nutrition to Lower Homocysteine Levels

Addressing high homocysteine through dietary modifications includes moderating alcohol and coffee consumption and adequately consuming foods rich in folate, vitamin B6, and vitamin B12. Some of the foods with the highest content of these vitamins are listed below:

  • Folate: spinach, liver, asparagus, and brussels sprouts
  • Vitamin B6: fish, organ meats, potatoes, non-citrus fruits
  • Vitamin B12: fish, meat, poultry, eggs, dairyΒ 

Eating a high-protein diet has also been shown to elevate homocysteine levels. Methionine is found in high quantities in the standard American diet, concentrated in foods like meat, fish, poultry, dairy, and eggs. Limiting the intake of these foods may prevent hyperhomocysteinemia.Β 

Supplements to Lower Homocysteine Levels

Dietary supplements may be required in addition to dietary modifications for correcting identified nutrient deficiencies. Studies have demonstrated the efficacy of B vitamin supplementation in reducing homocysteine levels; however, these studies have been unsuccessful at reducing cardiovascular disease risk. (5, 19, 42)Β 

Research suggests that omega-3 fatty acids effectively reduce homocysteine levels, especially when simultaneously dosed with B vitamins. The exact mechanisms by which omega-3 fatty acids influence homocysteine metabolism are not fully understood, but it is believed that they might impact the enzymes involved in the methionine-homocysteine cycle. (26)Β 

Oral N-acetyl cysteine (NAC) supplementation may be considered for preventing vascular events and treating hyperhomocysteinemia. Four weeks of oral NAC dosed at 1.8 grams daily resulted in reductions of serum homocysteine by 11.7% and significant reductions in systolic and diastolic blood pressure. (14)Β 

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Summary

Homocysteine is an amino acid naturally found in the blood that is involved in essential methylation reactions. Individuals with hyperhomocysteinemia (levels greater than 15 Β΅mol/L) may have an increased risk of cardiovascular and neurological conditions. Measuring and monitoring homocysteine levels, therefore, can be an important aspect of preventive healthcare. Working with a functional medicine provider to create personalized treatment plans, including nutritional, supplemental, and lifestyle interventions, helps to optimize homocysteine levels by addressing the root causes related to the elevation.

Homocysteine is an amino acid derived from the metabolism of methionine, an essential amino acid obtained from the diet. In the body, homocysteine can be converted into other amino acids or recycled back to methionine with the help of certain B vitamins. Elevated levels of homocysteine in the blood are associated with an increased risk of cardiovascular and neurological health issues. Maintaining optimal homocysteine levels is important for overall health, as high levels can contribute to inflammation and affect blood vessels.

Elevated homocysteine levels can indicate potential vitamin deficiencies or genetic factors that may affect the body's ability to metabolize this amino acid properly. By identifying and addressing the root causes of elevated homocysteine, healthcare practitioners can develop personalized nutrition plans and supplementation strategies that may help maintain healthy homocysteine levels and support overall wellness. Understanding the importance of homocysteine in functional medicine allows healthcare providers to implement proactive measures, promoting overall wellness and supporting the prevention of serious health conditions.

[signup]

The Biochemical Role of Homocysteine

Homocysteine is a sulfur-containing amino acid produced through the metabolism of methionine, an essential amino acid obtained from the diet. Homocysteine is involved in methylation, the transfer of a methyl group from one molecule to another. Methylation reactions are involved in numerous biological processes, including gene expression, protein function, neurotransmitter synthesis, and detoxification. (32, 43)

The body tightly regulates the homocysteine levels in the body through the methionine-homocysteine cycle. Methionine is converted to S-adenosylmethionine (SAMe). SAMe, often called the body's universal methyl donor, donates its methyl group to various substrates and is converted to S-adenosylhomocysteine (SAH). SAH is then converted to homocysteine. (31)Β 

Homocysteine has two possible fates. It can be remethylated to methionine in a reaction that requires vitamin B12 and folate. Alternatively, it can enter the transsulfuration pathway to be converted to cysteine, a reaction that requires vitamin B6 and leads to the synthesis of glutathione. (32, 43)Β 

A balance between these pathways is essential for maintaining proper levels of methionine and homocysteine in the body. Disruptions in this cycle can lead to elevated homocysteine levels (hyperhomocysteinemia). High homocysteine levels are associated with an increased risk for cardiovascular, cerebrovascular, and thromboembolic health issues. Therefore, understanding how homocysteine is produced in the body and its role in the methylation cycle is essential for maintaining proper biochemical balance and overall health. (32)Β 

Source: ResearchGate

Why Test for Homocysteine?

Serum homocysteine can be measured with a simple blood test. It can also be helpful to measure homocysteine in the context of a more comprehensive methylation panel, which measures other analytes involved in the methylation cycle and can help identify nutritional deficiencies contributing to abnormal homocysteine levels.Β 

Homocysteine increases as we age. Studies have found elevated homocysteine levels in almost 30% of people older than 65 and more than 40% in people 80 and older. This is relevant to aging and wellness because hyperhomocysteinemia has long been established as a risk factor for ischemic heart health issues, heart attack, sudden cardiac events, premature coronary artery conditions, carotid artery narrowing, blood clots, stroke, and peripheral vascular concerns. Newer studies have also identified high homocysteine as an independent risk factor for cognitive health issues; homocysteine levels higher than 15 Β΅mol/L are associated with nearly double the prevalence of cognitive decline. A 2017 study showed that patients with Parkinson's disease and cognitive dysfunction were more likely to have higher homocysteine levels.Β 

By measuring homocysteine levels, healthcare providers can assess your risk factors, identify possible vitamin deficiencies, and develop targeted interventions to support healthy levels. Addressing elevated homocysteine through dietary changes, supplements, and lifestyle modifications may help support your overall health. Regular testing allows for proactive health management, aiding in the support of overall well-being.

Understanding Homocysteine Test Results

Normal and optimal homocysteine levels should be less than 10 Β΅mol/L. Levels between 10-15 Β΅mol/L are considered borderline. (15) Hyperhomocysteinemia is diagnosed with a serum homocysteine level greater than 15 Β΅mol/L. There are three classifications of hyperhomocysteinemia, as follows (32):Β 

  • Moderate: 16-30 Β΅mol/L
  • Intermediate: 31-100 Β΅mol/L
  • Severe: > 100 Β΅mol/L

In a study of over 57,000 American adults, 1.8% of individuals had intermediate or severe hyperhomocysteinemia. This same study found that patients with homocysteine greater than 30 Β΅mol/L were more likely to have hypothyroidism, kidney health issues, and a prescription for an antidepressant, opioid, steroid, or thyroid hormone medication. (29)Β 

Causes of Elevated Homocysteine Levels

Elevated homocysteine levels do not necessarily mean you have a cardiovascular or neurological condition. Factors that can affect homocysteine metabolism and contribute to elevated levels include (16, 43):

  • Comorbid medical conditions: cancer, diabetes, kidney health issues, thyroid dysfunction, homocystinuriaΒ 
  • Folate, vitamin B6, and vitamin B12 deficiencies
  • Dietary factors: excess consumption of alcohol, coffee, and methionine-rich foods
  • Genetic variations of the cystathionine Ξ²-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR) genes
  • Older age
  • Male sex
  • Sedentary lifestyle
  • Smoking

Health Implications of High Homocysteine

Elevated levels of homocysteine may affect the inner endothelial lining of blood vessels, potentially contributing to inflammation and oxidative stress in the vasculature. This may increase the risk of atherosclerosis, a thickening and hardening of arteries caused by plaque buildup, and blood clots. Atherosclerosis is a primary concern for cardiovascular health, including coronary artery conditions (CAD), heart attack, heart failure, and stroke. (32)Β 

Studies show that nutritional interventions with homocysteine-lowering B vitamins may support brain health in elderly individuals with mild cognitive concerns. It is unclear if homocysteine directly causes brain changes or if these findings are related to vitamin deficiencies. Nevertheless, the evidence does suggest that homocysteine may affect brain health and blood flow to the brain. Elevated levels are associated with neurodegeneration progression, as observed in conditions like Alzheimer's disease. (32)Β 

There is also a correlation between high homocysteine levels and mood concerns. In a study including over 900 middle-aged men, researchers found that individuals in the upper tertile for homocysteine levels had more than a two-fold increased risk for mood concerns than those in the lowest tertile. Another study found that individuals with homocysteine levels greater than 12 Β΅mol/L had significantly lower SAMe, mood-enhancing neurotransmitters, and red blood cell folate levels.Β 

Osteoporosis and hip fracture are correlated with elevated homocysteine. Not only does homocysteine promote oxidative stress, but it may also interfere with collagen cross-linking, altering the bone matrix composition and potentially increasing bone fragility. (3)Β 

Strategies to Support Healthy Homocysteine Levels

If you have been diagnosed with hyperhomocysteinemia, the fortunate news is that there are many natural ways to support healthy homocysteine levels. Dietary factors that contribute to high homocysteine may be addressed through dietary modifications and supplementation. However, it's important to remember that increasing your intake of vitamins does not wholly reduce the risk of chronic health issues. In addition to the therapeutic interventions discussed below, you can support your heart and neurological health by quitting smoking, managing blood pressure and diabetes, getting adequate sleep, and exercising regularly.Β 

Nutrition to Support Healthy Homocysteine Levels

Addressing high homocysteine through dietary modifications includes moderating alcohol and coffee consumption and adequately consuming foods rich in folate, vitamin B6, and vitamin B12. Some of the foods with the highest content of these vitamins are listed below:

  • Folate: spinach, liver, asparagus, and brussels sprouts
  • Vitamin B6: fish, organ meats, potatoes, non-citrus fruits
  • Vitamin B12: fish, meat, poultry, eggs, dairyΒ 

Eating a high-protein diet has also been shown to elevate homocysteine levels. Methionine is found in high quantities in the standard American diet, concentrated in foods like meat, fish, poultry, dairy, and eggs. Limiting the intake of these foods may help manage homocysteine levels.Β 

Supplements to Support Healthy Homocysteine Levels

Dietary supplements may be required in addition to dietary modifications for correcting identified nutrient deficiencies. Studies have demonstrated the efficacy of B vitamin supplementation in reducing homocysteine levels; however, these studies have been unsuccessful at reducing cardiovascular disease risk. (5, 19, 42)Β 

Research suggests that omega-3 fatty acids may help support healthy homocysteine levels, especially when simultaneously dosed with B vitamins. The exact mechanisms by which omega-3 fatty acids influence homocysteine metabolism are not fully understood, but it is believed that they might impact the enzymes involved in the methionine-homocysteine cycle. (26)Β 

Oral N-acetyl cysteine (NAC) supplementation may be considered for supporting vascular health and managing homocysteine levels. Four weeks of oral NAC dosed at 1.8 grams daily resulted in reductions of serum homocysteine by 11.7% and significant reductions in systolic and diastolic blood pressure. (14)Β 

[signup]

Summary

Homocysteine is an amino acid naturally found in the blood that is involved in essential methylation reactions. Individuals with hyperhomocysteinemia (levels greater than 15 Β΅mol/L) may have an increased risk of cardiovascular and neurological conditions. Measuring and monitoring homocysteine levels, therefore, can be an important aspect of preventive healthcare. Working with a healthcare provider to create personalized plans, including nutritional, supplemental, and lifestyle interventions, helps to support healthy homocysteine levels by addressing the root causes related to the elevation.

The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
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Lab Tests in This Article

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2. Anderson, S. (2022, May 19). 6 Preventable Risk Factors Associated With Heart Attacks. Rupa Health. https://www.rupahealth.com/post/5-things-to-do-after-a-heart-attack

3. Bhardwaj, A., Sapra, L., Verma, B., et al. (2022). Homocysteine Metabolism in Health and Disease. Springer, Singapore. https://doi.org/10.1007/978-981-16-6867-8_4

4. Bottiglieri, T. (2000). Homocysteine, folate, methylation, and monoamine metabolism in depression. Journal of Neurology, Neurosurgery & Psychiatry, 69(2), 228–232. https://doi.org/10.1136/jnnp.69.2.228

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6. Cloyd, J. (2023, May 1). A Functional Medicine Protocol for Coronary Artery Disease. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-protocol-for-coronary-artery-disease

7. Cloyd, J. (2023, June 19). A Functional Medicine Post Stroke Protocol: Testing, Therapeutic Diet, and Integrative Therapy Options. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-post-stroke-protocol-testing-supplements-and-integrative-therapy-options

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13. Haan, M. N., Miller, J. W., Aiello, A. E., et al. (2007). Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging. The American Journal of Clinical Nutrition, 85(2), 511–517. https://doi.org/10.1093/ajcn/85.2.511

14. Hildebrandt, W., Sauer, R., Bonaterra, G., et al. (2015). Oral N-acetylcysteine reduces plasma homocysteine concentrations regardless of lipid or smoking status. The American Journal of Clinical Nutrition, 102(5), 1014–1024. https://doi.org/10.3945/ajcn.114.101964

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17. Huang, T., Zheng, J., Chen, Y., et al. (2011). High consumption of Ξ©-3 polyunsaturated fatty acids decrease plasma homocysteine: A meta-analysis of randomized, placebo-controlled trials. Nutrition, 27(9), 863–867. https://doi.org/10.1016/j.nut.2010.12.011

18. Khakham, C. (2023, April 6). Understanding Your Risk of Cardiovascular Disease With Functional Medicine Labs. Rupa Health. https://www.rupahealth.com/post/understanding-your-risk-of-cardiovascular-disease-with-functional-medicine-labs

19. Maruyama, K., Eshak, E. S., Kinuta, M., et al. (2019). Association between vitamin B group supplementation with changes in % flow-mediated dilatation and plasma homocysteine levels: a randomized controlled trial. Journal of Clinical Biochemistry and Nutrition, 64(3), 243–249. https://doi.org/10.3164/jcbn.17-56

20. Matthews, R. (2022, October 10). MTHFR Gene Variants: Diagnosis & Treatment. Rupa Health. https://www.rupahealth.com/post/mthfr-gene-variants-diagnosis-treatment

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22. Neibling, K. (2023, April 26). Complementary and Integrative Medicine Treatments for Hypertension and Cardiovascular Disease. Rupa Health. https://www.rupahealth.com/post/complementary-and-integrative-medicine-treatments-for-hypertension-and-cardiovascular-disease

23. Neibling, K. (2023, May 1). The Importance of Sleep for Cardiovascular Health. Rupa Health. https://www.rupahealth.com/post/the-importance-of-sleep-for-cardiovascular-health

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Peer Reviewed Journal
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The American Journal of Psychiatry
Peer Reviewed Journal
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Diabetes Care
Peer Reviewed Journal
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The Journal of the American College of Cardiology (JACC)
Peer Reviewed Journal
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The Journal of Clinical Oncology (JCO)
Peer Reviewed Journal
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Journal of Clinical Investigation (JCI)
Peer Reviewed Journal
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Circulation
Peer Reviewed Journal
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JAMA Internal Medicine
Peer Reviewed Journal
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PLOS Medicine
Peer Reviewed Journal
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Annals of Internal Medicine
Peer Reviewed Journal
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Nature Medicine
Peer Reviewed Journal
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The BMJ (British Medical Journal)
Peer Reviewed Journal
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The Lancet
Peer Reviewed Journal
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Journal of the American Medical Association (JAMA)
Peer Reviewed Journal
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Pubmed
Comprehensive biomedical database
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Harvard
Educational/Medical Institution
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Cleveland Clinic
Educational/Medical Institution
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Mayo Clinic
Educational/Medical Institution
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The New England Journal of Medicine (NEJM)
Peer Reviewed Journal
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Johns Hopkins
Educational/Medical Institution
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