Dietary/nutritional supplement guidelines for those with Ehlers-Danlos Syndrome, by

DIET & SUPPLEMENT GUIDELINES FOR PERSONS WITH EHLERS-DANLOS SYNDROME !Page 1 of 3!

Many persons with Ehlers-Danlos Syndrome (EDS) suffer moderate to severe (or even profound) gastrointestinal (GI) problems such as dysmotility, dysbiosis, and malabsorption, and significant malnutrition typically develops as a result. Additionally, many persons with EDS experience varying degrees of increased gut wall permeability or gut wall inflammation, and, as a result, many persons with EDS suffer secondary issues which may be remote to the gut, such as musculoskeletal pain, changes in bone density and mineralization, neurological or neuropsychological problems, focal or systemic inflammation, poor wound healing, and immune dysregulation, including autoimmune issues. The dietary inclusions/exclusions and nutritional supplementation guidelines in this document are generalized guidelines aimed specifically at supporting nutrition, maintaining normal gut bacterial balance, reducing increased gut permeability, and minimizing any symptoms attributable to gut inflammation or immune dysregulation, including abnormal mast cell activation.

REGARDING AN IDEAL !DIET FOR PERSONS WITH EDS: • NO CONCENTRATED/ADDED SUGARS OR BAD !CARBS. Learn what good !carbs are.

• ABSOLUTELY NO ARTIFICIAL SWEETENERS, such as aspartame (NutraSweet), neotame, advantame, sucralose, acesulfame potassium, or saccharin.

• NATURALLY OCCURRING !SUGARS in honey, molasses, brown sugar, coconut sugar, cane or beet sugar MAY BE CONSUMED IN MODERATION. Ideally, naturally occurring sugars should be as minimally processed and as close to their natural state as possible.

• ABSOLUTELY NO HIGH FRUCTOSE CORN SYRUP (HFCS). Look closely at labels, including condiments, seasonings, and dressings. If fructose is listed, it is often HFCS. Learn where HFCS is hidden.

• AVOID AGAVE. Why? Although agave extract is a natural !source of fructose, most processing methods used to bring agave extract to market for individual consumption yield a syrup that ranges from 55 to 97 percent fructose. (By comparison, HFCS averages 55 percent fructose.) Additionally, commercial agave processing most often involves the use of caustic chemicals in a process which is highly similar to the process by which cornstarch is converted into HFCS. Those who choose to use agave as a source of naturally occurring fructose are advised to purchase agave from providers committed to working ethically with indigenous people to obtain organic agave which is free of pesticides, processing agave extract at low temperatures, and ensuring the final agave product is about 50% free fructose not conjugated or bonded to other sugars.

• NO NATURAL !NON-SUGAR SWEETENER should be substituted for glucose, sucrose, or fructose. Examples of natural ! non-sugar sweeteners include stevia, monkfruit extract, sorbitol, lactitol, and xylitol.

• NO GLUTEN. Gluten is in wheat and wheat flour. Wheat protein is often gluten-derived. It may be necessary to read in detail about strict gluten-free diets in order to know how to avoid gluten in restaurants as well as at the market. Learn where gluten is hidden. Look closely at labels. Wheat is NOT the only grain, and wheat flour is NOT the only flour. Realize that eliminating gluten from your diet does NOT require you to shop exclusively in the gluten-free !section of the grocery store. Living gluten free does not have to cost a fortune. Living gluten free is less about figuring out how to emulate gluten with other ingredients (e.g. finding or making the perfect gluten-free cupcake or bagel) and more about learning to choose foods which are intrinsically more nutrient-dense and less harmful to your health. Put down the donut and the breakfast cereal, and eat your greens!

• EAT PROBIOTIC FOODS DAILY to address and prevent dysbiosis. Must-have: KEFIR (cultured milk). Most persons with lactose intolerance can easily tolerate kefir, as it is 99% lactose-free. (If dairy intolerance or dairy allergy is an issue, consider high-quality broad-spectrum prescription probiotics such as VSL#3.) Other probiotic foods include sauerkraut, kimchi, miso, tempeh, kombucha, buttermilk, yogurt, and kefir made from goat s milk/water/coconut milk.

• Ample intake of PREBIOTICS will boost the benefits of probiotic foods. Traditional dietary sources of prebiotics include beans, chicory root, dandelion greens, Jerusalem artichoke, asparagus, garlic, leeks, onion, raw oats, unrefined barley, and bananas. Supplemental prebiotics include inulin, FOS, XOS, GOS, and lactulose.

• To ADDRESS AND PREVENT DYSBIOSIS, in addition to above guidelines, avoid fried, grilled, and toasted foods, reduce intake of cured meat, limit alcohol consumption, and minimize polypharmacy as much as possible. Some persons are prone to significant gut inflammation and associated dysbiosis due to their particular intolerance of casein (in dairy), gluten (in wheat), or zein (in corn), and such individuals can only achieve and maintain normobiosis with strict avoidance of the offending protein source.

• EAT REAL FOOD. Take most (if not all) protein from organic and non-GMO vegetable, seed, or nut sources, aim for a lowglycemic index diet, eat organic fruit in moderation, eat healthy oils and fats, limit red meat intake, eat foods rich in antioxidants, and be certain to eat a diet sufficiently varied to include all essential !vitamins, minerals, and amino acids. The Paleolithic Diet, Mediterranean Diet, Whole Food Diet or Raw Food Diet, and balanced vegetarian/vegan diets generally approximate this approach. Ideally, If not following a vegan diet, use only organically-raised, vegetarian-fed, antibiotic-free, hormone-free, non-GMO, non-feedlot dairy, eggs, meat, and wild-caught game and fish. Cheese, butter, yogurt, cream, etc., can be a good source of protein, fat, and calcium, as long as there is no true dairy allergy.

2015 Heidi A. Collins, MD

!Last Updated: March 25, 2015!

DIET & SUPPLEMENT GUIDELINES FOR PERSONS WITH EHLERS-DANLOS SYNDROME !Page 2 of 3!

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NEVER EAT LONG SHELF-LIFE PROCESSED OR PRESERVED FOODS. AVOID ALL ARTIFICIAL FLAVORS AND COLORS. NO PLAIN !MILK AS A BEVERAGE. Humans as a species are the only mammals that decidedly and systematically collect the milk of another mammal for consumption, and a considerable debate exists as to whether this is healthy. The conventional belief that milk is a mandatory or exemplary source of specific vital nutrients is now widely challenged by a growing body of scientific evidence. If you must !drink milk, organic whole milk, lactose-free milk, and/or trusted raw milk are preferred to non-organic reduced-fat cow s milk. Better alternatives are goat s milk or plant-based milk !such as coconut milk, almond milk, or cashew milk, as long as they are not blended with filler ingredients (e.g. carrageenan).

LIBERALIZE SALT (unless specifically hypertensive). Do not adhere to the wide proclamation that salt is bad !for everyone. While salt should be avoided by a very large portion of the general population, most persons with EDS require a liberal intake of salt (specifically sodium). If not using iodized salt, ensure the diet contains adequate amounts of iodine. Sea salt is a popular alternative to traditional table salt, but keep in mind that many sea salt products are not adequately labeled regarding specific proportions of the cations and anions they contain, and heavy sea salt users may be at risk of specific electrolyte imbalances.

REGARDING INDIVIDUALIZED NEEDS FOR DIETARY EXCLUSIONS: • Avoidance of histamine-containing or histamine-releasing foods may be specifically necessary for some persons with EDS who are particularly sensitive to them. Of note, if dysbiosis is properly addressed, histamine tolerance may improve. Additionally, if the diet supports production of diamine oxidase (or diamine oxidase is supplemented), histamine tolerance may improve.

• Avoidance of fermented foods may be specifically necessary for some persons with EDS who are particularly sensitive to them. This may make it challenging to include dietary probiotics, which are typically fermented. Of note, many people will tolerate kefir, even if they do not tolerate most fermented foods.

• Avoidance of nightshade vegetables may be specifically necessary for some persons with EDS who are particularly sensitive to them. Nightshade vegetables mainly include potatoes, tomatoes, peppers, eggplant, and paprika.

• Avoidance of monosodium glutamate (MSG) as both an additive and a naturally occurring food ingredient may be specifically necessary for some persons with EDS who are particularly sensitive to it. Learn where MSG is hidden.

• It is reasonable and may be necessary for persons with EDS to consider exclusion diets, depending upon individual circumstances, as long as essential nutrients are not eliminated. For example, in addition to individualized exclusionary diet modifications mentioned above (e.g. Dairy-free, Lactose-free, Corn-free, Low Histamine, No Fermented Foods, No Nightshade Vegetables, No MSG, etc.), some persons with EDS have to follow Low Fructose, Anti-Inflammatory , Low FODMAP, or Elimination Diets. Some diets such as the GAPS Diet are particularly controversial but have been followed with reported success.

• Ultimately, formal testing for food allergies is warranted for many persons with EDS and may be essential for determining foods which must be eliminated. In the severest of cases, e.g. eosinophilic esophagitis, FPIES, etc., a very strict Elimination Diet may be necessary.

• Any restrictive diet MUST be reviewed with a physician and, ideally a nutritionist.

REGARDING SUPPLEMENTATION FOR PERSONS WITH EDS: • Many persons with EDS are found to be significantly deficient in numerous nutrients. Most notably, supplementation with magnesium, vitamin B6, vitamin D3, vitamin C, vitamin B12, zinc, and iron is often required. Other micronutrient deficiencies certainly occur.

• While magnesium deficiency is very often present, serum magnesium may be comfortably normal, despite severe bodily deficiency affecting the musculoskeletal, nervous, and other systems. Magnesium is very effectively empirically supplemented with chelated magnesium at one to two times the USRDA in patients who have no specific contraindication, such as renal failure. Magnesium is very well absorbed topically with use of magnesium oil or epsom salt soaks. Other forms of magnesium are too often poorly bio-available or poorly tolerated.

• Persons who struggle with hair shedding or breakage may benefit from supplementation specifically with L-lysine, vitamin C, vitamin B6, zinc, iron, and biotin.

• Persons struggling with symptoms of MCAD should consider taking quercetin, a well-documented mast cell stabilizing agent, in addition to intake of foods known to be rich in quercetin.

• Persons struggling with generalized or focal inflammation should consider taking curcumin formulated with piperine, in addition to foods known to be rich in curcumin and piperine. (Curcumin is abundant in turmeric, and piperine is abundant in black pepper.)

2015 Heidi A. Collins, MD

!Last Updated: March 25, 2015!

DIET & SUPPLEMENT GUIDELINES FOR PERSONS WITH EHLERS-DANLOS SYNDROME !Page 3 of 3!

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Persons who suffer nocturnal hypoglycemia may need to supplement !with glucose tablets or another immediate source of glucose such as glucose sport gels at night to address paroxysmal awakening with symptoms of hypoglycemia. A healthy, balanced, low-glycemic index bedtime snack may help to prevent nocturnal hypoglycemia and paroxysmal awakenings.

Whenever possible, any nutrient clinically suspected to be deficient or specifically demonstrated by testing to be deficient should be repleted by consistent dietary intake, rather than by resorting to taking a supplement. Some nutrients, such as magnesium and vitamin D, are far too difficult to reliably replete by diet alone and require supplementation in absorbable forms.

MULITVITAMINS ARE NOT RECOMMENDED. Instead, nutritional support and targeted supplementation is preferred, relying upon food intake for nutrients as much as possible, using supplements only when obtaining adequate food source would be too difficult.

The same guidelines for food should be applied to supplements. Supplements should, ideally, be free of added sugars or sugar substitutes, gluten, preservatives, artificial flavors, or artificial colors, etc.

Some persons with EDS are particularly affected by gastrointestinal problems which alter fat digestion and ultimately cause difficulty with absorption of essential fat-soluble vitamins. Addressing apparent deficiencies of fat-soluble vitamins such as vitamin D or vitamin K may require special consideration by an involved clinician.

In the event that intake of a healthy diet, in combination with any necessary oral supplementation, does not bring about desired improvements in health as well as normalization of laboratory indicators of nutritional status, parenteral supplementation (e.g., by IV, by injection, or topically) MUST be considered.

ALL supplements use MUST be shared (and, ideally, thoughtfully reviewed and discussed) with any involved physician!

When a health care provider reviews prescription and non-prescription (over-the-counter) medications during visits, all supplements, whether they be oral, topical, pill, powder, oil, herb, syrup, etc., should be regarded and discussed as medications.

Side effects and drug-drug or drug-food interactions of all prescription medications should be thoughtfully reviewed and considered on an individual basis, taking into account whether a person may need specific diet modification such as inclusions, exclusions, or nutrient supplementation in response to their specific prescription use. Ideally, everyone should carry a clearly written list of all prescription and non-prescription medications and supplements and their usual dosage, as well as a list of any allergies to medications, supplements, and foods, and any environmental or seasonal allergies.

RECOMMENDED DOSING FOR SPECIFIC SUPPLEMENTS OFTEN USED BY PERSONS WITH EDS: • Magnesium as CHELATED MAGNESIUM: 400 to 800mg in the morning as a supplement, with food.

• Vitamin B6 as Vitamin B6 or P5P : 5mg daily through food, OR up to 50mg daily as a supplement.

• Vitamin D3 (cholecalciferol) in a gel or oil form: 5,000iu in the morning as a supplement, with food, during non-summer months (or year-round, if not getting any significant direct sunlight or if consistently using sunblock). Vitamin D-25,OH level should be checked every 6-12 months, and dosage should be adjusted accordingly.

• Vitamin C: 3 to 6g (3,000 to 6,000mg) daily through food or as a supplement, with no more than 2,500mg taken in any single supplement dose.

• Vitamin B12: 100% of USRDA in food or as a supplement.

• Zinc: 100% of USRDA in food or as a supplement.

• Iron: 100% of USRDA in food or as a highly bioavailable supplement, such as ferrous fumarate or ferrous gluconate. Of note, absorption of iron is aided by co-administration of Vitamin C. • Quercetin: per bottle instructions. Use plain quercetin !no additional ingredient is needed.

• Curcumin/Piperine: per bottle instructions.

• Glucose tablets: While many foods or fluids can address acute hypoglycemia, the least expensive chewable generic glucose tablet in the smallest size is fine for use specifically to address acute hypoglycemic episodes and may be most convenient to have very nearby, to limit the effort expended to raise blood glucose quickly.

• Sodium Chloride: Of note, some persons with EDS who would benefit from increased salt intake are salt averse or simply find it difficult to get enough salt from their healthy diet. Supplementation with buffered salt tablets (e.g. ThermoTabs) is an effective and typically well-tolerated means of increasing sodium intake.

Any persons following these guidelines are, of course, encouraged and advised to review them with their involved healthcare provider(s) for further consideration, including whether specific testing such as laboratory measurement of baseline nutritional status, immunologic function, or other indicators of health/disease, followed by surveillance/re-testing is warranted.!

2015 Heidi A. Collins, MD

!Last Updated: March 25, 2015!