Oncology
|
June 28, 2023

Complementary and Integrative Medicine Treatment for Cancer Related Fatigue

Written By
Dr. Sonia Malani ND, FABNO
Medically Reviewed by
Updated On
September 17, 2024

The mental toll that comes with a cancer diagnosis is exhausting. Suddenly, your mind is in overdrive: "Have I found the right oncologist? Should I get a second opinion? How did I get cancer? What should I eat? How will I make it through chemotherapy?"

On top of the mental toll, there is a real physical toll that cancer treatment takes on patients. During treatment, the majority of cancer patients experience nausea, fatigue, hair loss, changes in appetite, and fatigue. Debilitating and overwhelming fatigue. Fatigue is seen in more than 80% of cancer patients. This fatigue can translate into a sharp decline in quality of life as patients may not have the energy to go to work, continue their hobbies, or see family and friends. So what can be done? Let's dive in.

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What is Cancer Related Fatigue (CRF)?

Cancer Related Fatigue (CRF) is defined as a persistent and distressing sense of exhaustion related to either cancer itself or cancer treatment that interferes with daily activities. This fatigue is usually not relieved by rest and can be felt even after a night of adequate sleep. Some patients may feel too tired to eat, shower, or get out of bed. For many patients, this fatigue can persist after treatment and into their survivorship years. One in four survivors of adolescent and young adult (AYA) cancers experience chronic fatigue up to 30 years after their diagnosis. In adult survivors, chronic fatigue has been reported in up to 49% of survivors.

Fatigue is different from weakness as weakness is usually due to loss of muscle strength. This can be a contributing factor to the fatigue of a cancer patient. However, fatigue can be present in the absence of weakness.

What Causes Cancer Related Fatigue (CRF)?

The etiology of CRF is multifactorial and, unfortunately, can be difficult to pinpoint. During active treatment like chemotherapy, fatigue can be a result of treatment side effects (low blood counts, electrolyte disturbances, nausea/vomiting, loss of appetite, etc.). Cancer tumors itself can release inflammatory proteins, known as cytokines, which are thought to cause fatigue. The anxiety and depression that accompanies many diagnoses can also play a role in fatigue. Additionally, pre-existing comorbidities can result in higher levels of reported fatigue during treatment.

A known side effect of radiation is also fatigue which can greatly impact the overall quality of life. Radiation-induced fatigue (RIF) can be long-lasting for those who undergo localized radiation. RIF has been associated with decreased cognitive function, sleep disturbances, less physical activity, and depression. RIF may be related to mitochondrial changes. However, the mechanism behind RIF is not completely understood.

Functional Medicine Labs That Can Help Individualize Treatment for Patients With Cancer Related Fatigue (CRF)

Screening for cancer related fatigue and contributing factors has become a major focus of supportive oncologic care. The workup for patients who are undergoing active treatment versus those who are in survivorship varies. Potentially treatable causes of fatigue should be addressed in those undergoing active treatment and can be screened for using the following labs.

Complete Blood Count

A complete blood count (also known as CBC) takes a look at white blood cells, red blood cells, hemoglobin, hematocrit, and platelets. When you don't have adequate amounts of red blood cells or hemoglobin to transport oxygen around the body, your body can feel extra tired. Decreased red blood cells or hemoglobin is known as anemia. A CBC can be used as a tool to screen for anemia. Anemia is a common side effect of cancer treatment and can be a contributing factor to CRF.  

Comprehensive Metabolic Panel

A Comprehensive Metabolic Profile (or CMP) is a common and helpful test that measures the chemical balance and metabolism of your body. This test can provide information on electrolyte shifts (sodium, chloride, potassium, and bicarbonate) as well as kidney and liver function and blood glucose levels. A common symptom of electrolyte imbalance or poorly managed blood sugar is fatigue, and therefore this test can be used to quickly evaluate if there are other causes of fatigue in a cancer patient.

Thyroid Stimulating Hormone

Many cancer survivors who complete treatment experience persistent fatigue. In survivorship, fatigue needs to be looked at comprehensively to make sure that there is not an underlying condition that is being missed. A common symptom of an underactive thyroid is fatigue. Testing thyroid stimulating hormone (or TSH) can be used as a screening tool for thyroid dysfunction. There can be utility to testing TSH during cancer treatment, as underdiagnosed hypothyroidism can make cancer related fatigue worse.

[signup]

Conventional Treatment for Cancer Related Fatigue (CRF)

During cancer treatment, both pharmaceutical and non-pharmaceutical interventions are recommended for CRF. The most common pharmaceuticals prescribed are stimulants, corticosteroids, and antidepressants.

The studies around stimulant efficacy have variable conclusions, and therefore a therapeutic trial is recommended to see how a patient responds. For example, out of at least eight published randomized controlled trials, only two have concluded that a stimulant like methylphenidate has a significantly better impact than a placebo on CRF.

Antidepressants can be helpful when the patient has both fatigue and depression. Screening tools for both anxiety and depression should be utilized when assessing CRF.  

Corticosteroids can be used for CRF, but they carry risks with long-term use. These risks involve bone loss, bruising, slower wound healing, and elevations in blood sugar (which could result in diabetes).

Complementary and Integrative Medicine for Cancer Related Fatigue (CRF)

There are many non-pharmaceutical interventions for CRF. These are becoming more commonly suggested by both oncologists and palliative specialists. The interventions range from exercise and nutrition to acupuncture and supplements.

Nutrition and Dietary Interventions for Cancer Related Fatigue

Adequate nutrition is a nuanced conversation during active cancer treatment. Treatment-related side effects like nausea, vomiting, and loss of appetite need to be addressed properly before making dietary recommendations. Additionally, when patients are experiencing high levels of fatigue, they may feel too tired to cook or even eat. Therefore, when discussing nutrition, the provider should zoom out and make sure that not only dietary recommendations are provided but also that the patient has access to groceries and that they have help in preparing meals. Sometimes a therapeutic suggestion could be a meal service where the meals are nutritionally dense and delivered right to the patient's door. An intervention may also be helping the patient place an online order to have groceries delivered to their home.

In regards to dietary suggestions: increased protein may help prevent muscle loss during treatment. The Mediterranean diet and other plant-based diets can decrease overall inflammation and may reduce fatigue.

Supplements and Herbs That Are Helpful for Combating Cancer Related Fatigue

There are many botanical medicines that can help improve energy levels during treatment. Quality, dose, and frequency matter, so make sure you are working with a skilled professional on supplement recommendations.

American Ginseng

Ginseng is a very popular traditional Chinese medicine. Patients undergoing active cancer treatment with moderate-to-severe fatigue can try ginseng to help with CRF. In a systematic review and meta-analysis from 2021, ginseng did show improvements in CRF when compared to control. There were five randomized controlled trials that were reviewed, two studies used American Ginseng 2000mg for eight weeks, and three studies used Asian red ginseng 400mg-3000mg for 4-12 weeks. It is important to screen patients to make sure they aren't on a drug that will interact unfavorably with ginseng, such as anticoagulants.

Mistletoe Extract

Mistletoe extract comes from the plant Viscum album L. (also known as European Mistletoe) and can be helpful in CRF. European mistletoe has been utilized in cancer care for close to 100 years in German-speaking countries. In a systematic review and meta-analysis from 2022, mistletoe extracts reduce CRF when compared to control in randomized controlled trials. In the US, mistletoe is still used mostly in an investigational setting. Mistletoe is administered via a subcutaneous injection two to three times a week. Mistletoe can help stimulate an immune response which can decrease inflammatory markers and decrease the risk of neutropenia-related fatigue. Mistletoe should be monitored closely and done under the supervision of a trained clinician.

Melatonin (Long Term Use)

Most people associate melatonin with sleep. However, in a recent clinical trial, 92 breast cancer patients were randomly assigned to either receive melatonin (18 mg/day) or placebo from 1 week before the adjuvant treatments until two years after their completion. The levels of fatigue were assessed before and after intervention using Brief Fatigue Inventory (BFI). After the intervention of melatonin, the breast cancer patients in the melatonin group reported a lower fatigue score. Melatonin use after the completion of cancer treatment can be helpful in decreasing fatigue levels.

Benefits of Exercise in Managing Cancer Related Fatigue

The ASCO (American Society of Clinical Oncology) recommends that cancer survivors with fatigue aim for 150 minutes of moderate aerobic exercise (e.g., fast walking, cycling, or swimming) per week with an additional two to three strength training (e.g., weight lifting) sessions per week unless contraindicated. Asking patients who are exhausted to move may feel counterintuitive, but sedentary habits can lead to muscle loss which can lead to worse functional status. Encourage patients to join a walking club or fitness class at their local gym to encourage both movement and community.

Acupuncture And Traditional Chinese Medicine As An Adjunct Therapy For Cancer Related Fatigue

Traditional Chinese Medicine (TCM) is widely accepted as a mainstream therapy alongside cancer treatment in China and has been for thousands of years. In a recent 2020 meta-analysis and systematic review, a total of 23 trials involving 1832 participants identified with cancer-related fatigue were included to assess the effectiveness and safety of TCM therapy for CRF. Twenty trials reported a beneficial effect of TCM therapy on CRF. TCM is safe and effective and should be utilized alongside cancer treatment to help reduce side effects like CRF.

Integrating CIM Approaches with Conventional Treatment

Many patients are seeking out complementary and integrative approaches to help increase their quality of life and decrease the side effects of their cancer treatment. Integrative Oncology is a growing field of healthcare specialists who can guide patients on safe and effective ways to incorporate integrative treatment with their conventional cancer treatment. As a patient, it is important to keep communication open and transparent with your conventional oncology team. Inform them of the therapies that you are thinking of trying or may have already started so that they can make sure they are compatible with your primary cancer treatment.

[signup]

Summary

Cancer-related fatigue is a common side effect of cancer and can feel debilitating and overwhelming. CRF can persist long after treatment is complete. The good news is that it is possible to use integrative medicine to alleviate or lessen CRF. CRF is multifactorial in origin and, therefore, should be looked at comprehensively. Physicians should be screening for anemia, poor nutritional status, sleep disturbances, anxiety, or depression, as these can all be contributing factors to CRF. Many botanical and traditional medicines can improve CRF as well as nutrition and lifestyle changes. If you are experiencing CRF, find an integrative oncologist to join your care team and create a personalized treatment plan.

The mental toll that comes with a cancer diagnosis can be overwhelming. Suddenly, your mind is in overdrive: "Have I found the right oncologist? Should I get a second opinion? How did I get cancer? What should I eat? How will I make it through chemotherapy?"

On top of the mental toll, there is a real physical toll that cancer treatment takes on patients. During treatment, many cancer patients experience nausea, fatigue, hair loss, changes in appetite, and fatigue. Debilitating and overwhelming fatigue. Fatigue is seen in more than 80% of cancer patients. This fatigue can translate into a decline in quality of life as patients may not have the energy to go to work, continue their hobbies, or see family and friends. So what can be done? Let's explore some options.

[signup]

What is Cancer Related Fatigue (CRF)?

Cancer Related Fatigue (CRF) is defined as a persistent and distressing sense of exhaustion related to either cancer itself or cancer treatment that interferes with daily activities. This fatigue is usually not relieved by rest and can be felt even after a night of adequate sleep. Some patients may feel too tired to eat, shower, or get out of bed. For many patients, this fatigue can persist after treatment and into their survivorship years. One in four survivors of adolescent and young adult (AYA) cancers experience chronic fatigue up to 30 years after their diagnosis. In adult survivors, chronic fatigue has been reported in up to 49% of survivors.

Fatigue is different from weakness as weakness is usually due to loss of muscle strength. This can be a contributing factor to the fatigue of a cancer patient. However, fatigue can be present in the absence of weakness.

What Causes Cancer Related Fatigue (CRF)?

The causes of CRF are multifactorial and can be difficult to pinpoint. During active treatment like chemotherapy, fatigue can be a result of treatment side effects (low blood counts, electrolyte disturbances, nausea/vomiting, loss of appetite, etc.). Cancer tumors themselves can release inflammatory proteins, known as cytokines, which are thought to contribute to fatigue. The anxiety and depression that accompanies many diagnoses can also play a role in fatigue. Additionally, pre-existing comorbidities can result in higher levels of reported fatigue during treatment.

A known side effect of radiation is also fatigue which can greatly impact the overall quality of life. Radiation-induced fatigue (RIF) can be long-lasting for those who undergo localized radiation. RIF has been associated with decreased cognitive function, sleep disturbances, less physical activity, and depression. RIF may be related to mitochondrial changes. However, the mechanism behind RIF is not completely understood.

Functional Medicine Labs That Can Help Individualize Treatment for Patients With Cancer Related Fatigue (CRF)

Screening for cancer related fatigue and contributing factors has become a major focus of supportive oncologic care. The workup for patients who are undergoing active treatment versus those who are in survivorship varies. Potentially manageable causes of fatigue should be addressed in those undergoing active treatment and can be screened for using the following labs.

Complete Blood Count

A complete blood count (also known as CBC) takes a look at white blood cells, red blood cells, hemoglobin, hematocrit, and platelets. When you don't have adequate amounts of red blood cells or hemoglobin to transport oxygen around the body, your body can feel extra tired. Decreased red blood cells or hemoglobin is known as anemia. A CBC can be used as a tool to screen for anemia. Anemia is a common side effect of cancer treatment and can be a contributing factor to CRF. Β 

Comprehensive Metabolic Panel

A Comprehensive Metabolic Profile (or CMP) is a common and helpful test that measures the chemical balance and metabolism of your body. This test can provide information on electrolyte shifts (sodium, chloride, potassium, and bicarbonate) as well as kidney and liver function and blood glucose levels. A common symptom of electrolyte imbalance or poorly managed blood sugar is fatigue, and therefore this test can be used to quickly evaluate if there are other causes of fatigue in a cancer patient.

Thyroid Stimulating Hormone

Many cancer survivors who complete treatment experience persistent fatigue. In survivorship, fatigue needs to be looked at comprehensively to make sure that there is not an underlying condition that is being missed. A common symptom of an underactive thyroid is fatigue. Testing thyroid stimulating hormone (or TSH) can be used as a screening tool for thyroid function. There can be utility to testing TSH during cancer treatment, as underdiagnosed hypothyroidism can make cancer related fatigue worse.

[signup]

Conventional Treatment for Cancer Related Fatigue (CRF)

During cancer treatment, both pharmaceutical and non-pharmaceutical interventions are considered for CRF. The most common pharmaceuticals prescribed are stimulants, corticosteroids, and antidepressants.

The studies around stimulant efficacy have variable conclusions, and therefore a therapeutic trial is often considered to see how a patient responds. For example, out of at least eight published randomized controlled trials, only two have concluded that a stimulant like methylphenidate has a significantly better impact than a placebo on CRF.

Antidepressants can be helpful when the patient has both fatigue and depression. Screening tools for both anxiety and depression should be utilized when assessing CRF. Β 

Corticosteroids can be used for CRF, but they carry risks with long-term use. These risks involve bone loss, bruising, slower wound healing, and elevations in blood sugar (which could result in diabetes).

Complementary and Integrative Medicine for Cancer Related Fatigue (CRF)

There are many non-pharmaceutical interventions for CRF. These are becoming more commonly suggested by both oncologists and palliative specialists. The interventions range from exercise and nutrition to acupuncture and supplements.

Nutrition and Dietary Interventions for Cancer Related Fatigue

Adequate nutrition is a nuanced conversation during active cancer treatment. Treatment-related side effects like nausea, vomiting, and loss of appetite need to be addressed properly before making dietary recommendations. Additionally, when patients are experiencing high levels of fatigue, they may feel too tired to cook or even eat. Therefore, when discussing nutrition, the provider should zoom out and make sure that not only dietary recommendations are provided but also that the patient has access to groceries and that they have help in preparing meals. Sometimes a therapeutic suggestion could be a meal service where the meals are nutritionally dense and delivered right to the patient's door. An intervention may also be helping the patient place an online order to have groceries delivered to their home.

In regards to dietary suggestions: increased protein may help prevent muscle loss during treatment. The Mediterranean diet and other plant-based diets can decrease overall inflammation and may support reduced fatigue.

Supplements and Herbs That Are Helpful for Combating Cancer Related Fatigue

There are many botanical medicines that may help improve energy levels during treatment. Quality, dose, and frequency matter, so make sure you are working with a skilled professional on supplement recommendations.

American Ginseng

Ginseng is a very popular traditional Chinese medicine. Patients undergoing active cancer treatment with moderate-to-severe fatigue might consider ginseng to help with CRF. In a systematic review and meta-analysis from 2021, ginseng showed improvements in CRF when compared to control. There were five randomized controlled trials that were reviewed, two studies used American Ginseng 2000mg for eight weeks, and three studies used Asian red ginseng 400mg-3000mg for 4-12 weeks. It is important to screen patients to make sure they aren't on a drug that will interact unfavorably with ginseng, such as anticoagulants.

Mistletoe Extract

Mistletoe extract comes from the plant Viscum album L. (also known as European Mistletoe) and may be helpful in CRF. European mistletoe has been utilized in cancer care for close to 100 years in German-speaking countries. In a systematic review and meta-analysis from 2022, mistletoe extracts were found to reduce CRF when compared to control in randomized controlled trials. In the US, mistletoe is still used mostly in an investigational setting. Mistletoe is administered via a subcutaneous injection two to three times a week. Mistletoe may help stimulate an immune response which can decrease inflammatory markers and decrease the risk of neutropenia-related fatigue. Mistletoe should be monitored closely and done under the supervision of a trained clinician.

Melatonin (Long Term Use)

Most people associate melatonin with sleep. However, in a recent clinical trial, 92 breast cancer patients were randomly assigned to either receive melatonin (18 mg/day) or placebo from 1 week before the adjuvant treatments until two years after their completion. The levels of fatigue were assessed before and after intervention using Brief Fatigue Inventory (BFI). After the intervention of melatonin, the breast cancer patients in the melatonin group reported a lower fatigue score. Melatonin use after the completion of cancer treatment may be helpful in decreasing fatigue levels.

Benefits of Exercise in Managing Cancer Related Fatigue

The ASCO (American Society of Clinical Oncology) recommends that cancer survivors with fatigue aim for 150 minutes of moderate aerobic exercise (e.g., fast walking, cycling, or swimming) per week with an additional two to three strength training (e.g., weight lifting) sessions per week unless contraindicated. Asking patients who are exhausted to move may feel counterintuitive, but sedentary habits can lead to muscle loss which can lead to worse functional status. Encourage patients to join a walking club or fitness class at their local gym to encourage both movement and community.

Acupuncture And Traditional Chinese Medicine As An Adjunct Therapy For Cancer Related Fatigue

Traditional Chinese Medicine (TCM) is widely accepted as a mainstream therapy alongside cancer treatment in China and has been for thousands of years. In a recent 2020 meta-analysis and systematic review, a total of 23 trials involving 1832 participants identified with cancer-related fatigue were included to assess the effectiveness and safety of TCM therapy for CRF. Twenty trials reported a beneficial effect of TCM therapy on CRF. TCM is considered safe and effective and may be utilized alongside cancer treatment to help reduce side effects like CRF.

Integrating CIM Approaches with Conventional Treatment

Many patients are seeking out complementary and integrative approaches to help increase their quality of life and decrease the side effects of their cancer treatment. Integrative Oncology is a growing field of healthcare specialists who can guide patients on safe and effective ways to incorporate integrative treatment with their conventional cancer treatment. As a patient, it is important to keep communication open and transparent with your conventional oncology team. Inform them of the therapies that you are thinking of trying or may have already started so that they can make sure they are compatible with your primary cancer treatment.

[signup]

Summary

Cancer-related fatigue is a common side effect of cancer and can feel debilitating and overwhelming. CRF can persist long after treatment is complete. The good news is that it is possible to use integrative medicine to alleviate or lessen CRF. CRF is multifactorial in origin and, therefore, should be looked at comprehensively. Physicians should be screening for anemia, poor nutritional status, sleep disturbances, anxiety, or depression, as these can all be contributing factors to CRF. Many botanical and traditional medicines may improve CRF as well as nutrition and lifestyle changes. If you are experiencing CRF, consider finding an integrative oncologist to join your care team and create a personalized treatment plan.

The information in this article is designed for educational purposes only and is not intended to be a substitute for informed medical advice or care. This information should not be used to diagnose or treat any health problems or illnesses without consulting a doctor. Consult with a health care practitioner before relying on any information in this article or on this website.

Learn more

Lab Tests in This Article

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  • Servaes, P., Verhagen, S., & Bleijenberg, G. (2002). Determinants of chronic fatigue in disease-free breast cancer patients: a cross-sectional study. Annals of oncology: official journal of the European Society for Medical Oncology, 13(4), 589–598. https://doi.org/10.1093/annonc/mdf082
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  • Savina, S., & Zaydiner, B. (2019). Cancer-Related Fatigue: Some Clinical Aspects. Asia-Pacific journal of oncology nursing, 6(1), 7–9. https://doi.org/10.4103/apjon.apjon_45_18
  • Bruera, E., Valero, V., Driver, L., Shen, L., Willey, J., Zhang, T., & Palmer, J. L. (2006). Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 24(13), 2073–2078. https://doi.org/10.1200/JCO.2005.02.8506
  • Inglis, J. E., Lin, P. J., Kerns, S. L., Kleckner, I. R., Kleckner, A. S., Castillo, D. A., Mustian, K. M., & Peppone, L. J. (2019). Nutritional Interventions for Treating Cancer-Related Fatigue: A Qualitative Review. Nutrition and cancer, 71(1), 21–40. https://doi.org/10.1080/01635581.2018.1513046
  • Oei, S. L., Thronicke, A., & Schad, F. (2019). Mistletoe and Immunomodulation: Insights and Implications for Anticancer Therapies. Evidence-based complementary and alternative medicine: eCAM, 2019, 5893017. https://doi.org/10.1155/2019/5893017
  • Pelzer, F., Loef, M., Martin, D. D., & Baumgartner, S. (2022). Cancer-related fatigue in patients treated with mistletoe extracts: a systematic review and meta-analysis. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer, 30(8), 6405–6418. https://doi.org/10.1007/s00520-022-06921-x
  • Najafi, T. F., Bahri, N., Tohidinik, H. R., Feyz, S., Bloki, F., Savarkar, S., & Jahanfar, S. (2021). Treatment of cancer-related fatigue with ginseng: A systematic review and meta-analysis. Journal of Herbal Medicine, 28, 100440. https://doi.org/10.1016/j.hermed.2021.100440
  • Sedighi Pashaki, A., Sheida, F., Moaddab Shoar, L., Hashem, T., Fazilat-Panah, D., Nemati Motehaver, A., Ghanbari Motlagh, A., Nikzad, S., Bakhtiari, M., Tapak, L., Keshtpour Amlashi, Z., Javadinia, S. A., & Keshtpour Amlashi, Z. (2023). A randomized, controlled, parallel-group, trial on the long-term effects of melatonin on fatigue associated with breast cancer and its adjuvant treatments. Integrative Cancer Therapies, 22, 153473542311686. https://doi.org/10.1177/15347354231168624
  • Zhao, Y., Wang, S., Li, J., Zhou, Y., Wu, W., & Swei Sunny, H. (2020). Effectiveness and safety of traditional Chinese medical therapy for cancer-related fatigue: a systematic review and Meta-analysis of randomized controlled trials. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan, 40(5), 738–748. https://doi.org/10.19852/j.cnki.jtcm.2020.05.003
  • LucΓ­a, A., Earnest, C., & PΓ©rez, M. (2003). Cancer-related fatigue: can exercise physiology assist oncologists?. The Lancet. Oncology, 4(10), 616–625. https://doi.org/10.1016/s1470-2045(03)01221-x
  • Schad, F., Thronicke, A., von Trott, P., & Oei, S. L. (2020). Analysis of Changes in Cancer-Related Fatigue of Breast Cancer Patients Receiving an Integrative Medicine Program. Integrative cancer therapies, 19, 1534735420963780. https://doi.org/10.1177/1534735420963780
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Hey practitioners! πŸ‘‹ Join Dr. Chris Magryta and Dr. Erik Lundquist for a comprehensive 6-week course on evaluating functional medicine labs from two perspectives: adult and pediatric. In this course, you’ll explore the convergence of lab results across different diseases and age groups, understanding how human lab values vary on a continuum influenced by age, genetics, and time. Register Here! Register Here.

Hey practitioners! πŸ‘‹ Join Dr. Terry Wahls for a 3-week bootcamp on integrating functional medicine into conventional practice, focusing on complex cases like Multiple Sclerosis. Learn to analyze labs through a functional lens, perform nutrition-focused physical exams, and develop personalized care strategies. Register Here.

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