Managing Hypermobile Ehlers-Danlos Syndrome: A Naturopathic Approach to Whole-Body Wellness

Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder primarily characterized by joint hypermobility, chronic pain, and a range of other systemic symptoms. Though often underdiagnosed, hEDS can have a significant impact on a patient's quality of life. Naturopathic medicine offers a holistic approach to managing hEDS, focusing on treating the whole person and addressing underlying issues.

What is hEDS?

Ehlers-Danlos Syndromes (EDS) are a group of heritable connective tissue disorders affecting collagen, a key protein that provides structure and strength to various tissues in the body. Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most common subtype, marked by joint hypermobility, musculoskeletal pain, and frequent dislocations or subluxations. In addition to joint-related symptoms, patients with hEDS may experience:

• Gastrointestinal issues (e.g. irritable bowel syndrome – IBS)

• Dysautonomia (e.g. postural orthostatic tachycardia syndrome – POTS)

• Fatigue and sleep disturbances

• Easy bruising and poor wound healing

• Anxiety and mood disorders

The condition can vary widely in its severity, from mild joint hypermobility to disabling chronic pain and multi-systemic issues. Diagnosis of hEDS is primarily clinical, relying on a combination of patient history, physical examination, and established criteria.

Conventional Management of hEDS

Conventional treatment of hEDS often involves a multidisciplinary approach, including physical therapy, pain management, and medications to control symptoms. While these interventions can help manage some aspects of the condition, many patients seek additional support to address the chronic and systemic nature of hEDS. This is where naturopathic medicine can offer valuable adjunctive care.

Naturopathic Approach to hEDS

Naturopathic doctors (NDs) focus on treating the underlying causes of disease while emphasizing lifestyle changes, natural therapies, and patient education. For hEDS patients, a naturopathic approach includes:

1. Nutritional Support

   An anti-inflammatory diet incorporating omega-3 fatty acids to help reduce systemic inflammation can be helpful in managing chronic pain associated with hEDS. Other essential nutrients to include are vitamin C (a key co-factor in collagen synthesis) and zinc (important for tissue repair and immune function).

2. Digestive Health

   Irritable bowel syndrome (IBS) is a common symptom in patients with hEDS, utilizing probiotics to maintain a balanced gut microbiome, recommending a high fiber diet to support gut motility and identify and eliminating food sensitives can also be beneficial for patients with hEDS to reduce inflammation within the body and alleviate symptoms of IBS.

3. Movement

   Exercise programs that focus on low-impact activities and emphasize gentle, controlled movements to support muscle recovery and alleviate pain would be ideal for patients with hEDS.

4. Nervous System Support

   Using mind-body practices such as meditation, yoga and/or breathing exercises can support the autonomic regulation and reduce anxiety and pain perception in patients with hEDS. Adaptogenic herbs has also been shown to help modulate the body’s stress response.

5. Pain Management

   Anti-inflammatory herbs such as ginger, turmeric or Boswellia can help reduce inflammation and pain. Acupuncture has also been beneficial for some patients who experience chronic pain from hEDS.

6. Sleep Optimization

   Sleep disturbances can be common in patients with hEDS. Utilizing herbal supports and nutraceuticals such as passionflower and magnesium can help promote relaxation and improve quality of sleep in hEDS patients.

Hypermobile Ehlers-Danlos Syndrome is a complex condition that affects multiple body systems. While conventional management is crucial for stabilizing joints and managing acute symptoms, naturopathic medicine offers a comprehensive approach that addresses the underlying causes, supports overall health, and empowers patients with hEDS to take an active role in their care. Through nutritional support, digestive health optimization, nervous system regulation, pain management and sleep optimization, NDs can help patients with hEDS improve their quality of life and manage symptoms more effectively.

 In health,

Dr. Sami Leung, ND

References:

1. Castori, M., Morlino, S., Pascolini, G., Blundo, C., & Grammatico, P. (2015). Gastrointestinal and nutritional issues in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. American journal of medical genetics. Part C, Seminars in medical genetics, 169C(1), 54–75. https://doi.org/10.1002/ajmg.c.31431

2. Chopra, P., Tinkle, B., Hamonet, C., Brock, I., Gompel, A., Bulbena, A., & Francomano, C. (2017). Pain management in the Ehlers-Danlos syndromes. American journal of medical genetics. Part C, Seminars in medical genetics, 175(1), 212–219. https://doi.org/10.1002/ajmg.c.31554

3. Demes, J. S., McNair, B., & Taylor, M. R. G. (2020). Use of complementary therapies for chronic pain management in patients with reported Ehlers-Danlos syndrome or hypermobility spectrum disorders. American journal of medical genetics. Part A, 182(11), 2611–2623. https://doi.org/10.1002/ajmg.a.61837

4. Do, T., Diamond, S., Green, C., & Warren, M. (2021). Nutritional Implications of Patients with Dysautonomia and Hypermobility Syndromes. Current nutrition reports, 10(4), 324–333. https://doi.org/10.1007/s13668-021-00373-1

5. Doyle, T. A., & Halverson, C. M. E. (2022). Use of complementary and alternative medicine by patients with hypermobile Ehlers-Danlos Syndrome: A qualitative study. Frontiers in medicine, 9, 1056438. https://doi.org/10.3389/fmed.2022.1056438

6. Guedry, S. E., Langley, B. O., Schaefer, K., & Hanes, D. A. (2024). Integrative medicine for hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS): a feasibility study. Disability and rehabilitation, 1–14. Advance online publication. https://doi.org/10.1080/09638288.2024.2314713

7. Hakim, A. (2004). Hypermobile Ehlers-Danlos Syndrome. In M. P. Adam (Eds.) et. al., GeneReviews®. University of Washington, Seattle.

8. Heds Body System. The Ehlers Danlos Society. (2024, September 12). https://www.ehlers-danlos.com/heds/

9. Langevin, H. M., Churchill, D. L., Wu, J., Badger, G. J., Yandow, J. A., Fox, J. R., & Krag, M. H. (2002). Evidence of connective tissue involvement in acupuncture. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 16(8), 872–874. https://doi.org/10.1096/fj.01-0925fje

10. Mantle, D., Wilkins, R. M., & Preedy, V. (2005). A novel therapeutic strategy for Ehlers-Danlos syndrome based on nutritional supplements. Medical hypotheses, 64(2), 279–283. https://doi.org/10.1016/j.mehy.2004.07.023

11. Pullar, J. M., Carr, A. C., & Vissers, M. C. M. (2017). The Roles of Vitamin C in Skin Health. Nutrients, 9(8), 866. https://doi.org/10.3390/nu9080866

12. Topan, R., Pandya, S., Williams, S., Ruffle, J. K., Zarate-Lopez, N., Aziz, Q., & Fikree, A. (2024). Comprehensive Assessment of Nutrition and Dietary Influences in Hypermobile Ehlers-Danlos Syndrome-A Cross-Sectional Study. The American journal of gastroenterology, 119(4), 727–738. https://doi.org/10.14309/ajg.0000000000002586

13. Song, B., Yeh, P., Nguyen, D., Ikpeama, U., Epstein, M., & Harrell, J. (2020). Ehlers-Danlos Syndrome: An Analysis of the Current Treatment Options. Pain physician, 23(4), 429–438.

Love the Skin You're In

Your skin is the largest organ in your body. It protects and gives you signals from the environment, and regulates temperature and water. We often don’t think about the functions of our skin until it starts to cause us problems – itching, rashes, acne, discoloration, premature aging, etc – all of which can be a signal of something deeper going on in our body. The skin is also a great absorptive surface, for better or for worse. We can use this effect to our benefit for absorbing certain medications or nutrients applied topically (eg. estrogen, testosterone, magnesium), though the absorptive nature of skin also makes us susceptible to adverse effects from environmental exposures that may be allergic or irritant in nature.

ouTSIDE IN VS AND INSIDE OUT

Whether it’s limiting exposures to harmful substances, or increasing exposure to therapeutic agents, both internal and external approaches can, and should, be used in conjunction to promote optimal skin health.

outside in

Skin & The Immune System —> Allergies

An allergic response occurs when the immune system reacts abnormally to a substance found in the environment. The substance that provokes the reaction is called an allergen.

3 Categories of Allergens:

• Ingested allergens - reactions to food or things consumed orally

• Inhaled allergens - reactions to substances we breathe in

• Contact allergens - reactions to substances applied on skin or mucus membranes (lips, mouth, groin)

Skin Allergies

1. Allergic reactions tend to happen after repeated exposure to a substance. The reaction never happens to the first exposure because the immune system must first become sensitized to the chemical.

2. Once you have been sensitizes, you will always be allergic to it.

3. Sudden development of allergies is possible.

4. Even small amounts of allergen can trigger a reaction that can last for several weeks.

5. With each new exposure, the reaction becomes stronger.

6. The reaction can spread beyond the exposure site.

7. A reaction need not happen immediately - it can take hours or days to present.

Allergy Testing

• Prick testing - for allergens ingested or inhaled

• Patch testing - for contact allergens

Top Allergens in Personal Care Products

1. Fragrances

2. Preservatives

3. Hair dyes

4. Lanolin

5. Synthetic detergents

6. Botanicals

7. Nail cosmetics

8. Sunscreens

Skin and The Immune System —> Irritants & Intolerances

Skin irritants elicit non-allergy reactions, that may be immediate, dose-dependent, and/or cumulative.

Irritant Reactions

• Irritation is dose-dependent - the more you are exposed, the more severe the reaction.

• Irritation is cumulative - multiple exposures, multiple chemicals.

• Irritation can happen after a single exposure.

• Irritation does not necessarily happen after every exposure (cumulative exposures impact the outcome).

• An irritant reaction can happen immediately after exposures and can resolve quickly after exposure ends.

Top Irritants in Personal Care Products

1. Water

2. Soap and detergents

3. Fragrances

4. Botanicals

5. Alcohol

6. Abrasive scrubs

7. Vitamin A derivatives and Alpha-Hydroxy Acid (AHA)

8. Shampoos and conditioners

inside out

Your skin is also reflective of what is going on within your body. We see this often with certain conditions that have dermatologic manifestations, such as Celiac disease (dermatitis herpetiformis), systemic lupus erythematosus (malar erythema), PCOS (acne) and many others. Aside from diagnosable pathologies, functional imbalances and other factors can also impact the quality and health of our skin. These may include:

• Inflammation

• Hormonal imbalances

• Diet

• Digestive issues

• Food sensitivities

• Sun exposure

• Stress

• Nutrient deficiencies

• Immune dysfunction

• Medications or supplements

• Smoking

• Infections

Skin problems are often multifactorial, and as such often require a multi-factorial approach. Whether you are addressing the symptoms of chronic disease or looking to improve the appearance and health of your skin overall, optimizing and correcting any one or several of these factors may be necessary to achieve desired results.

THE FIRST STEP TO TREATMENT IS A PROPER ASSESSMENT.

Deciding where to start can be overwhelming. With no shortage of information online, many times patients are confronted with information and option overload. A detailed history taking with a health professional can help to narrow down areas to focus on and get you started on a treatment plan tailored to your individual needs to help you love the skin you’re in.

In health,

Dr. Jacalyn Sieben, ND

PS - for more information about a holistic Outside-In approach I highly recommend the book referenced below.

Reference:

Skotnicki, S. (2018). Beyond soap: The real truth about what you are doing to your skin and how to fix it for a beautiful, healthy glow. Penguin Random House.

Probiotics, Your Microbiome and Your Mood

Have you ever noticed that what you eat impacts your mood? Have you felt worse after binging on junk food or after a night of drinking? There is compelling research suggesting that it may not be just the guilt talking - your microbiome may be contributing in a large way to the conversation.  

What is the microbiome?  

There are 10- to 100-trillion symbiotic microbes of various species existing in and around the human body, collectively referred to as the microbiome [1]. These friendly microbes outnumber your own human cells and have recently become popularized for the growing body of evidence detailing the vast impacts they have on human physiology and behaviour. 

The microbes in your intestines make vitamins, amino acids, hormones, neurotransmitters and other signaling molecules that impact the way your brain and body function [2], [3]. They also produce short-chain fatty acids as byproducts that your intestinal cells use for energy, which contributes to healthy gut function [3].  

These microbes live in our digestive tract and survive off the foods that we eat. Just like any other living organism, their health (and therefore ours) depends on consuming a healthy diet. It has been shown that dietary changes (e.g. from animal-based to plant-based), as well as any significant systemic stress and inflammation can alter the composition (i.e. diversity and abundance of species) of your microbiome within just 24 hours [3].  

Altered microbiome composition has been associated with many conditions, such as inflammatory bowel disease (IBD), psoriasis, atopic dermatitis, autoimmune arthritis, type 2 diabetes, obesity, and atherosclerosis [3]. This is not surprising given the significant role these organisms have in regulating metabolism and immunity. In fact, researchers are finding that the microbiome composition in a given disease seem to have a different complement of microbes associated with it. For example, an IBD microbiome has less diversity (fewer species of healthy microbes), and lower numbers of good bacterial species. Therefore, it has lower short-chain fatty acid production [3]. Short-chain fatty acids (SCFAs) are essential to the health of your intestinal cells and are also thought to be anti-inflammatory in the gut [3]. 

The Microbiome’s Effect on Mood & Behaviour  

Gut microbes relay messages to the brain via various direct and indirect mechanisms - bacterial metabolites, metabolic precursors, immune signalling, vagus nerve signalling, and Hypothalamic Pituitary-Adrenal axis activation [4], [5]. It is through these mechanisms that neurodevelopment or neurodegeneration are influenced [5]. A significant portion of the microbiome influence on the brain comes via the gut-brain axis: a bi-directional pathway connecting the nervous system in your digestive tract to the central nervous system (your brain) [4], [5]. As shown in the graphic below, your gut and your brain communicate directly via nerves that transmit different signals and molecules, which can have a profound effect both ways to both systems [6].

Photo credit: https://fhs.mcmaster.ca/forsythe-lab/microbiota_gut_brain_axis.html 

Considering the gut-brain axis and the physical manifestations that different microbiome composition can produce, it should be no surprise that there are mental/emotional implications as well. Many psychiatric and neurological pathologies have gastrointestinal co-morbidities, including schizophrenia, autism, neurodegenerative diseases, anxiety, and depression [7]. As noted above, different pathologies have different microbiome composition. This extends to mood and neurodegenerative disorders, such as major depressive disorder, schizophrenia, Parkinson’s disease, and autism spectrum disorder [2], [5], [8]. There is also data suggesting that alterations in the microbiome from addictions (e.g. alcohol, cocaine) may be associated with substance cravings and increased risk of developing associated psychiatric disorders, such as anxiety and depression [9], [10]. 

Probiotics & Your Mood 

Probiotics are supplements that contain healthy microbes that ,when ingested, influence the health of your microbiome. Probiotics used to benefit mood and cognition have been coined “psychobiotics,” and are a burgeoning new area of interest in research. A study by Tillisch et al. used brain scans (functional magnetic resonance imaging) to demonstrate the ability of probiotics to alter brain activity in areas associated with processing emotion and sensation, and to reduce negative thinking associated with sad mood [4], [7], [11], [12]. While most studies indicate that further research in this area is needed, associations between specific strains of microbial species and their benefits on various conditions are rapidly emerging [7], [13][14]. A recent human clinical trial of adjunctive probiotic intervention for Major Depressive Disorder (MDD) showed that compared with placebo, probiotic intervention exhibited greater improvement in depressive symptoms [15]. Participants who received the probiotic intervention experienced reductions in both depression and anxiety, and the probiotics were well-tolerated, prompting the authors to suggest probiotics as an acceptable adjunctive intervention for adults with MDD [15]. 

How Can I Support My Microbiome? 

Lifestyle 

A healthy lifestyle goes a long way in supporting your microbiome, and healthy eating is just one part of it. As mentioned earlier, dietary changes, significant systemic stress, and inflammation can alter your microbiome within just 24 hours. There are many different types of stress - physical, mental and emotional - that can lead to physiologic changes that can alter the microbiome. Practicing stress management through self-care, meditation, social connection, thoughtful schedule planning, getting adequate sleep, and setting appropriate boundaries with people and responsibilities will help you be more resilient in dealing with stress. The better you are at managing stress, the less likely it will spill over into added physical or mood-related symptoms.  

Digestive Supports 

Probiotics are a great start to improving your gut health and mood, though quality and potency matter!  Our naturopathic doctors are here to assess if and which type of probiotics are most suitable for you, as well as to review if any further testing or treatments are indicated to optimize your digestive and mental health.  

We are here to help, so reach out if you are looking for professional guidance! 

In Health,  

Dr. Jacalyn Sieben, ND 

[1] Ursell, L.K. et al. (2012). Defining the human microbiome. Nutrition Reviews. Vol. 70 (Suppl. 1):S38- S44. doi:10.1111/j.1753-4887.2012.00493.x

[2] Dinan, T.G. & Cryan, J.F. Mood by microbe: Towards clinical translation. Genome Medicine. 8:36. DOI  10.1186/s13073-016-0292-1

[3] Corfe, B.M. et al. (2015). The multifactorial interplay of diet, the microbiome, and appetite control:  current knowledge and future challenges. Proceedings of the Nutrition Society. 74, 235-244.  doi:10.1017/S0029665114001670

[4] Dinan, T.G., Stilling, R.M., Stanton, C., Cryan, J.F. (2015). Collective unconscious: How gut microbes shape human behavior. Journal of Psychiatric Research. 63:1-9. http://dx.doi.org/10.1016/ j.jpsychires.2015.02.021

[5] Sharon, G. et al. (2016). The central nervous system and the gut microbiome. Cell. 167. http:// dx.doi.org/10.1016/j.cell.2016.10.027

[6] McMaster University. (2019). The microbiota-gut-brain axis. [Digital Image] Retrieved from: https:// fhs.mcmaster.ca/forsythe-lab/microbiota_gut_brain_axis.html

[7] Sampson, T.R. & Mazmanian, S.K. (2015). Control of brain development, function, and behavior by the microbiome. Cell Host & Microbe. http://dx.doi.org/10.1016/j.chom.2015.04.011

[8] Jiang, H. et al. (2015). Altered fecal microbiota composition in patients with major depressive disorder. Brain, Behavior, and Immunity. 48:186-194. http://dx.doi.org/10.1016/j.bbi.2015.03.016

[9] Hillemacher, T., et al. (2018). Alcohol, microbiome, and their effect on psychiatric disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. Volume 85, Pages 105-115. https://doi.org/ 10.1016/j.pnpbp.2018.04.015

[10] Kiraly, D.D. et al. (2016). Alterations of the host microbiome affect behavioral responses to cocaine. Scientific Reports. 6:35455. DOI: 10.1038/srep35455

[11] Rea, K., Dinan, T.G., Cryan, J.F. (2016). The microbiome: A key regulator of stress and neuroinflammation. Neurobiology of Stress. 23-33. http://dx.doi.org/10.1016/j.ynstr.2016.03.001

[12] Tillisch, K., Labus, J., Kilpatrick, L., Jiang, Z., Stains, J., Ebrat, B., Guyonnet, D., Legrain-Raspaud, S., Trotin, B., Naliboff, B., et al. (2013). Consumption of fermented milk product with probiotic modulates brain activity. Gastroenter- ology 144, 1394–1401. DOI: https://doi.org/10.1053/j.gastro.2013.02.043

[13] Foster, J.A., Rinaman, L., & Cryan, J.F. (2017). Stress & the gut-brain axis: Regulation by the microbiome. Neurobiology of Stress. 124-136. http://dx.doi.org/10.1016/j.ynstr.2017.03.0 01

[14] Sarkar, A. et al. (2016). Psychobiotics and the manipulation of bacteria-gut-brain signals. Trends in Neurosciences. Vol 39, No. 11. http://dx.doi.org/10.1016/j.tins.2016.09.002

[15] Nikolova VL, Cleare AJ, Young AH, Stone JM. (2023). Acceptability, Tolerability, and Estimates of Putative Treatment Effects of Probiotics as Adjunctive Treatment in Patients with Depression: A Randomized Clinical Trial. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2023.1817

How Optimizing Gut Health Can Keep Your Cholesterol Levels in Check

First off, what is cholesterol anyway?

Cholesterol is a waxy, fat-like substance that is produced by your liver. Cholesterol is actually vital for many different structures and functions in the body such as the formation of cell membranes, hormone production, and the synthesis of vitamin D from the sun. So if it plays all of these key roles, why are we so concerned when cholesterol levels get high?

You may have heard by now that we have “good” (HDL) and “bad” (LDL) types of cholesterol. HDL and LDL stand for high density and low density lipoprotein. These are particles made from fat and protein that attach themselves to cholesterol to transport them throughout the blood stream. LDL is associated with the bad form of cholesterol as its function is to carry cholesterol to the arteries. When LDL levels get too high it may collect in vessel walls and contribute to plaque formation (atherosclerosis) in addition to increasing your risk of heart disease and stroke. HDL on the other hand functions by transporting cholesterol back to the liver – almost like a clean up crew- to prevent blood cholesterol levels from getting too high. So when cholesterol gets returned to the liver – what happens next? In the liver, cholesterol is secreted directly into bile where it is then secreted into the intestines. This is where optimizing gut health comes into play.

Once cholesterol reaches the intestines one of two things can happen. One, the bile is removed from the body via fecal excretion or two, the cholesterol is re-absorbed by enterocytes (cells that line our gut) and returned back to circulation. The intestine typically absorbs about 50% of the cholesterol presented to it – but this can vary from 20%-80% depending on the person. Of the absorbed cholesterol, approximately 80% comes from bile and only ~20% comes from diet (which is why eggs might not be so bad after all). Given that it seems our bodies own production and subsequent elimination of cholesterol seems to be the larger issue, how can we help swing our reabsorption percent from 50-80% down to 20%?

1. FIBER:

   • Soluble fiber can reduce the absorption of cholesterol into your blood stream. Insoluble fiber decreases intestinal transit time thus promoting regular bowel movements to ensure your LDL cholesterol is being eliminated efficiently. It is suggested to consume between 25-30g of fiber per day.

   • Soluble fiber foods: Brussels sprouts, avocados, flax seeds, and black beans

   • Insoluble fiber foods: nuts, beans and vegetables, such as cauliflower, green beans and potatoes

2. Probiotics:

• Probiotics are healthy bacteria found in our gut. Fermented foods contain them and fiber containing foods feed them. Probiotics are suggested to reduce cholesterol by deconjugating bile acids, using cholesterol for nourishment, and/or incorporating cholesterol into the cell wall of the probiotic bacteria. Probiotics also help to keep us regular which decreases the chance for cholesterol to become re-absorbed.

• Sources of probiotics: yogurt, sauerkraut, kimchi, kombucha, miso, tempeh, pickles.

Lastly, outside of gut health and moving more into diet in general, the Mediterranean diet has been shown to be an effective approach to supporting healthy cholesterol levels. The Mediterranean diet includes the following:

Increased Omega 3 consumption:

• Foods high in omega 3’s can increase HDL while reducing triglycerides — a type of fat found in blood — as well as reduce your blood pressure and risk of developing blood clots.

• Omega 3 rich foods: Fish and other seafood (especially cold-water fatty fish, such as salmon, mackerel, tuna, herring, and sardines) Nuts and seeds (such as flaxseed, chia seeds, and walnuts)

Increased consumption of Nuts/Seeds:

• Almonds and other tree nuts can improve blood cholesterol levels by reducing LDL. Almonds have been suggested to reduce LDL levels by reducing LDL reabsorption in the gut, increasing cholesterol and bile secretion into the gut, and regulating enzymes involved in cholesterol syntheses. 

Olive oil:

• Foods that contain monounsaturated fats (including olive oil) may raise HDL (good) cholesterol. The least processed form of olive oil to use is cold pressed extra virgin olive oil.

In health,

Dr. Brittany Pearce, ND., RHN.

References:

Vrins CL. From blood to gut: direct secretion of cholesterol via transintestinal cholesterol efflux. World J Gastroenterol. 2010;16(47):5953-5957. doi:10.3748/wjg.v16.i47.5953

Jesch ED, Carr TP. Food Ingredients That Inhibit Cholesterol Absorption. Prev Nutr Food Sci. 2017;22(2):67-80. doi:10.3746/pnf.2017.22.2.67

Freeman AM, Morris PB, Aspry K, Gordon NF, Barnard ND, Esselstyn CB, Ros E, Devries S, O'Keefe J, Miller M, Ornish D, Williams KA, Batts T, Ostfeld RJ, Litwin S, Aggarwal M, Werner A, Allen K, White B, Kris-Etherton P. A Clinician's Guide for Trending Cardiovascular Nutrition Controversies: Part II. J Am Coll Cardiol. 2018 Jul 31;72(5):553-568. doi: 10.1016/j.jacc.2018.05.030. PMID: 30049315.

Cohen DE. Balancing cholesterol synthesis and absorption in the gastrointestinal tract. J Clin Lipidol. 2008;2(2):S1-S3. doi:10.1016/j.jacl.2008.01.004

Cartolano FC, Dias GD, Miyamoto S, Damasceno NRT. Omega-3 Fatty Acids Improve Functionality of High-Density Lipoprotein in Individuals With High Cardiovascular Risk: A Randomized, Parallel, Controlled and Double-Blind Clinical Trial. Front Nutr. 2022 Feb 23;8:767535. doi: 10.3389/fnut.2021.767535. PMID: 35281761; PMCID: PMC8905646.

Berryman CE, Preston AG, Karmally W, Deckelbaum RJ, Kris-Etherton PM. Effects of almond consumption on the reduction of LDL-cholesterol: a discussion of potential mechanisms and future research directions. Nutr Rev. 2011 Apr;69(4):171-85. doi: 10.1111/j.1753-4887.2011.00383.x. PMID: 21457263.