All Posts by Melody Hartzler

Are you missing a key mineral in your diet?

I hope your summer is off to a great start. It’s definitely going to be a different kind of summer given the landscape of the pandemic. A good reason to make sure our bodies are fueled with proper nutritious foods and that we correct any nutrient depletions we may be experiencing. I get a lot of questions about magnesium, it’s such a powerful mineral in the body and one that unfortunately is depleted in our soil with modern farming practices. This post was written by Dr. Kristina Burban, PharmD who was an intern with us in April. We will be sharing part 2 later this week where we will discuss various forms of magnesium.

Dr. Hartzler

Magnesium is an essential mineral that plays a role in healthy cell function and bone structure. Sources of dietary magnesium include legumes, whole grains, vegetables, nuts, dark chocolate, fish, and beef.1 Magnesium deficiency is common in the United States; one study found that 68% of Americans do not consume the recommended amount (310-420 mg) of magnesium daily.2 Signs and symptoms of magnesium deficiency include muscle cramps, headaches, fatigue, mood changes, and irregular heartbeat1. Your provider can test blood magnesium level through a simple blood draw. Problems with absorbing magnesium or not enough intake of magnesium have been associated with developing osteoporosis, high blood pressure, diabetes, and heart disease.1 People commonly use magnesium for constipation or heartburn, but it can be useful for other reasons as well.

Benefits of Magnesium:

Heart health:

  • Having enough magnesium is important for heart health. Studies have shown various cardiac benefits with either dietary or supplemental magnesium. Magnesium intake has been shown to decrease stroke risk. Most of these studies looked at magnesium from dietary sources.3-8  In heart disease patients with low magnesium levels, taking magnesium supplements reduced heart pain. Also, heart disease patients with low magnesium levels had worse outcomes than heart disease patients with normal magnesium levels.Supplementing magnesium in coronary artery disease may help reduce blood clots.10  Patients who took 800-1200 mg magnesium oxide daily for 3 months had 35% less clots than patients who did not take magnesium.

 Diabetes:

  • Multiple studies show that increasing dietary magnesium reduces the risk of developing type 2 diabetes.11-14  A review combined and analyzed existing data about type 2 diabetes and magnesium in 2016. It found that more magnesium intake corresponded to less risk for developing type 2 diabetes. This study also found that increasing dietary magnesium by 100mg/day reduced the risk of developing type 2 diabetes by 8-13%.15 In people who have diabetes, there is evidence that taking magnesium can increase insulin sensitivity.16 

Metabolism:

  • Magnesium helps support a healthy metabolism. There is evidence that supplementing magnesium can reduce the risk of developing metabolic syndrome17, a combination of conditions including high blood pressure, blood sugar, body fat, and cholesterol. People with metabolic syndrome are more likely to have low magnesium levels.18  Studies have shown that taking supplementing magnesium can have slight benefits on blood pressure and cholesterol.19-23 A study of adults in the United States found that 68% consumed less than the recommended daily amount of 310-420 mg magnesium daily. Also, it found that people who didn’t consume enough magnesium were more likely to have inflammation. C-reactive protein, a marker of the body’s inflammation, was more likely to be elevated in those patients.2

Mental Health:

  • Through what we know about brain function, magnesium has a potential role in altering mood. GABA, a calming neurotransmitter, needs magnesium to be able to function properly in the brain. Magnesium can also change how glutamate, a neurotransmitter that excites, functions in the brain. Therefore, it must be important to have enough magnesium. 
  • Research suggests that magnesium could have benefits in anxiety.  One study tested a preparation of 300mg magnesium with hawthorn and poppy plant extracts in patients with anxiety disorders.  The group that took the magnesium preparation showed clinical improvement. 24 In a 2017 review of existing data, researchers found that 4 out of the 8 total clinical studies about magnesium and anxiety reported positive effects on anxiety outcomes.25 However, all of the studies tested a combination of ingredients, not magnesium by itself. More research is needed to establish the effectiveness of magnesium on reducing anxiety.
  • Clinical research about magnesium’s effects on depression are also promising, but limited. In animal studies, magnesium seems to have an antidepressant effect, but there is less evidence in humans. One study tested 2,000 mg magnesium daily for 6 weeks in patients with symptoms of depression. The study showed improvement in depression symptoms, but there was no placebo group and the patients knew they were taking magnesium, which could have affected the results.26  Another study tested supplementing 500 mg magnesium versus placebo in patients with depression and low magnesium levels. After 8 weeks, the patients taking magnesium showed improvement in depression status.27 Again, more research is needed to see how effective magnesium is in improving depression.
  • A national health and nutrition survey showed that people who report under 7 hours of sleep have lower intake of calcium, magnesium, and vitamin D.28 This reinforces how important it is to have enough mineral and vitamin intake, whether through dietary sources or supplementation. Overall, having enough magnesium is likely to help improve rest, relaxation, and mood. 
  • Magnesium is also helpful for sleep. In one particular study of insomnia in the elderly statistically significant increases in sleep time, sleep efficiency, and melatonin, and also resulted in significant decrease in time to sleep onset and serum cortisol concentration.29

References:

  1. Magnesium. In: Natural Medicines Comprehensive Database. Stockton, CA: Therapeutic Research Faculty. [Updated January 23, 2020]. 
  2. King DE, Mainous AG 3rd, Geesey ME, Woolson RF. Dietary magnesium and C-reactive protein levels. J Am Coll Nutr 2005;24:166-71.
  3. Adebamowo SN, Spiegelman D, Willett WC, Rexrode KM. Association between intakes of magnesium, potassium, and calcium and risk of stroke: 2 cohorts of US women and updated meta-analysis. Am J Clin Nutr. 2015;101(6):1269-77. 
  4. Suter PM. The effects of potassium, magnesium, calcium, and fiber on risk of stroke. Nutr Rev 1999;57:84-8.
  5. Ascherio A, Rimm EB, Hernan MA, et al. Intake of potassium, magnesium, calcium, and fiber and risk of stroke among US men. Circulation 1998;98:1198-204.
  6. Nie ZL, Wang ZM, Zhou B, Tang ZP, Wang SK. Magnesium intake and incidence of stroke: meta-analysis of cohort studies. Nutr Metab Cardiovasc Dis 2013;23(3):169-76.
  7. Xu T, Sun Y, Xu T, Zhang Y. Magnesium intake and cardiovascular disease mortality: a meta-analysis of prospective cohort studies. Int J Cardiol 2013;167(6):3044-7. 
  8. Zhang W, Iso H, Ohira T, Date C, Tamakoshi A; JACC Study Group. Associations of dietary magnesium intake with mortality from cardiovascular disease: the JACC study. Atherosclerosis 2012;221(2):587-95.
  9. Lasserre B, Spoerri M, Moullet V, et al. Should magnesium therapy be considered for the treatment of coronary heart disease? II. Epidemiological evidence in outpatients with and without coronary heart disease. Magnes Res 1994;7:145-53. 
  10. Shechter, M., Merz, C. N., Paul-Labrador, M., Meisel, S. R., Rude, R. K., Molloy, M. D., Dwyer, J. H., Shah, P. K., and Kaul, S. Beneficial antithrombotic effects of the association of pharmacological oral magnesium therapy with aspirin in coronary heart disease patients. Magnes.Res. 2000;13(4):275-284.
  11. Meyer KA, Kushi LH, Jacobs DR, et al. Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am J Clin Nutr 2000;71:921-30.
  12. Song Y, Manson JE, Buring JE, Liu S. Dietary magnesium intake in relation to plasma insulin levels and risk of type 2 diabetes in women. Diabetes Care 2004;27:59-65.
  13. Fung TT, Manson JE, Solomon CG, et al. The association between magnesium intake and fasting insulin concentration in healthy middle-aged women. J Am Coll Nutr 2003;22:533-8. 
  14. Lopez-Ridaura R, Willett WC, Rimm EB, et al. Magnesium intake and risk of type 2 diabetes in men and women. Diabetes Care 2004;27:134-40.
  15. Fang X, Han H, Li M, et al. Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies. Nutrients. 2016;8(11)
  16. Barbagallo M, Dominguez LJ. Magnesium and type 2 diabetes. World J Diabetes. 2015;6(10):1152‐1157. doi:10.4239/wjd.v6.i10.1152
  17. He K, Liu K, Daviglus ML, et al. Magnesium intake and incidence of metabolic syndrome among young adults. Circulation 2006;113:1675-82.
  18. Guerrero-Romero F, Rodriguez-Moran M. Low serum magnesium levels and metabolic syndrome. Acta Diabetol 2002;39:209-13. 
  19. Hoogerbrugge N, Cobbaert C, de Heide L, et al. Oral physiological magnesium supplementation for 6 weeks with 1 g/d magnesium oxide does not affect increased Lp(a) levels in hypercholesterolaemic subjects. Magnes Res 1996;9:129-32.
  20. Jee SH, Miller ER 3rd, Guallar E, et al. The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials. Am J Hypertens 2002;15:691-6.
  21. Dickinson HO, Nicolson DJ, Campbell F, et al. Magnesium supplementation for the management of essential hypertension in adults. Cochrane Database Syst Rev 2006;3:CD004640.
  22. Kass L, Weekes J, Carpenter L. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr 2012;66:411-8.
  23. Zhang X, Li Y, Del Gobbo LC, et al. Effects of magnesium supplementation on blood pressure: a meta-analysis of randomized double-blind placebo-controlled trials. Hypertension. 2016 Aug;68(2):324-33. 
  24. Hanus M, Lafon J, Mathieu M. Double-blind, randomised, placebo-controlled study to evaluate the efficacy and safety of a fixed combination containing two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium in mild-to-moderate anxiety disorders. Curr Med Res Opin 2004;20:63-71.
  25. Boyle NB, Lawton C, Dye L. The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A Systematic Review. Nutrients. 2017;9(5):429. Published 2017 Apr 26. doi:10.3390/nu9050429
  26. Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C. Role of magnesium supplementation in the treatment of depression: a randomized clinical trial. PLoS One. 2017 Jun 27;12(6):e0180067. 
  27. Rajizadeh A, Mozaffari-Khosravi H, Yassini-Ardakani M, Dehghani A. Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: A randomized, double-blind, placebo-controlled trial. Nutrition. 2017 Mar;35:56-60. doi: 10.1016/j.nut.2016.10.014. Epub 2016 Nov 9.
  28. Ikonte CJ, Mun JG, Reider CA, Grant RW, Mitmesser SH. Micronutrient Inadequacy in Short Sleep: Analysis of the NHANES 2005-2016. Nutrients. 2019 Oct 1;11(10). pii: E2335. doi: 10.3390/nu11102335. 
  29. Abbasi, et al. J Res Med Sci. 2012 Dec; 17(12): 1161–1169.

Homemade Marshmallows

With kids at home and the warm weather we’ve had in Ohio the last few weekends, it certainly feels like summer is here. We spent the day yesterday being outside. Hubby doing yard work and me playing with the kids. I did help clean up our outdoor furniture a bit, so I have somewhere to sit until we can budget for a new outdoor dining set. 🙂

We had some brush we needed to trim back in our yard and we attempted to burn it, well it didn’t work out so well, but we got enough of a fire going to have some S’mores! We also love these on apples. Just bake some apples with cinnamon and a little butter until tender, then put these on top for a healthy dessert. They were also a treat in my latte this morning.

I hope you all are staying home and staying healthy. Hopefully the warm weather sticks around and we can just have a really long summer with extra snuggle time, while we pray for those that are on the front lines.

Dr. Hartzler

Print Recipe
Homemade Marshmallows
Looking for a way to make S'mores or have some tasty marshmallows without corn syrup or refined sugar. Here is a great recipe. It was originally posted on a website called TGIpaleo.com but that site is no longer up. So I am posting here so everyone can still enjoy.
Course Dessert
Cuisine Paleo (Whole30)
Servings
Ingredients
Course Dessert
Cuisine Paleo (Whole30)
Servings
Ingredients
Instructions
  1. Pull out your stand mixer. I only use mine a few times per year but this is one of my recipes that it's super helpful! If that’s not an option, get a partner who is willing to hold an electric mixer while you pour the boiling honey into the gelatin. (Dustin has done this before when we've made this at his parents for our thanksgiving baked apples!)
  2. Place the gelatin in the bottom of a large mixing bowl. Pour 1/2 c water on top and whisk (with mixer) to combine, then set aside. Pour the honey and remaining 1/2 c water in a small saucepan over medium heat. Bring to a rolling boil, stirring to make sure it doesn’t burn or boil over.
  3. Turn on your mixer to medium-high in the bowl with the gelatin. SLOWLY pour a steady stream of hot honey, making sure the stream of liquid hits the side of the bowl first so it doesn’t curdle the gelatin. Keep pouring slowly until all everything is combined. Then leave the mixer on for 15 minutes. Yes 15 whole minutes. Add the vanilla about 2 minutes before it’s done.
  4. Grease a 9×13 inch pan with coconut oil or any other healthy oil. When the marshmallow cream is whipped to perfection, spread it into the pan. Refrigerate for at least 4 hours or overnight. Then cut into squares and use for all your marshmallow-y needs. Note: they still work great in S'mores if you do the aluminum foil packets and place by the fire, otherwise roasting them they will melt quickly so just be cautious and be ready with those graham crackers!
Recipe Notes

A couple options for grass-fed gelatin sources (thanks in advance for using my affiliate links!) 

Great Lakes Gelatin

Vital Proteins Beef Gelatin

For Graham Crackers,Pamela's Gluten Free have been the best we've tried. You can get them on Amazon or Thrive Market.

Share this Recipe

One Option for Stress & Anxiousness

I know with recent events, the anxiousness and stress level, especially among many of our front-line healthcare workers is high. I also know friends and family that are struggling with anxiousness as they continue to see the impact of this pandemic on our world. My pharmacy intern Sydney Schultz, wrote this post for you. I don’t think we knew how relevant it would be in this time. I hope you find it valuable and reach out if you have questions.

Dr. Hartzler

Anxiety disorders are one of the most common mental illnesses in the United States, affecting 40 million adults in the United States age 18 and older, or 18.1% of the population. Anxiety is an extremely prevalent condition worldwide that is associated with a high degree of morbidity and impairment of quality of life. Generalized anxiety disorder (GAD), according to the DSM 5 criteria, is characterized by excessive anxiety and worry occurring more days than not for at least six months.

Current standard of care for anxiety typically includes selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, sertraline and paroxetine as first line therapy, and benzodiazepines such as clonazepam, alprazolam and lorazepam for breakthrough anxiety. These medications are often times habit forming and associated with undesirable side effects such as sedation, impaired concentration and depression. Not to mention, it can be quite difficult to taper off these medications due to withdrawal effects. 

Lavandula angustifolia, on the other hand, is a non-habit forming, well-tolerated, natural supplement that has shown to be effective in relieving symptoms of anxiety, promoting quality of sleep and calming nerves.  Lavender has been used for centuries for its relaxing, calming and mood alleviating effects. In Germany, a monograph issued by the Federal Health Agency in 1978 approved lavender flowers, under the trademark name Silexan, for the treatment of restlessness. Whereas lavender products have historically been used as aromatherapy, Silexan™ is a novel preparation created through steam distillation from Lavandula angustifolia for oral use.

Silexan™ has been shown to be more effective than placebo and as effective as paroxetine and lorazepam (see table below). These trials utilized the Hamilton anxiety rating scale (HAM-A) to assess symptom relief. The HAM-A is a clinician rated scale that assesses symptoms of anxiety. Patients are rated based on the extent of their symptoms and physical manifestations of anxiety such as gastrointestinal and insomnia. 

TrialInclusion diagnosisDesignInterventionResults: Mean decrease in HAM-A
Kasper et al. (2010)Anxiety disorder, not otherwise specifiedDouble-blind, randomized, placebo-controlled80 mg/day Silexan™ (n=104) or placebo (n=108) for 10 weeks16.0 ±  8.3 (Silexan) 
9.5 ± 9.1 (Placebo)


Woelk and Schlaefke (2010)Generalized anxiety disorderDouble blind, double dummy, randomized, reference-controlled80 mg/day Silexan™ (n=40) or 0.5 mg/day Lorazepam (n=37) for 6 weeks11.3 ± 6.7 (Silexan) 
11.6 ± 6.6 (Lorazepam)


Kasper et al. (2014)Generalized anxiety disorderDouble blind, randomized, reference-controlled, placebo-controlled 160 mg/day Silexan™ (n=121), 80 mg/day Silexan™ (n=135), 20 mg/day paroxetine (n=132) or placebo (n=135) for 10 weeks 14.1 ± 9.3 (Silexan 160)
12.8 ± 8.7 (Silexan 80)
11.3 ± 8.0 (paroxetine) 
9.5 ± 9.0 (placebo)


Kasper et al. 
(2016)


Mixed anxiety/depressive disorderDouble-blind, randomized, placebo-controlled80 mg Silexan™ (n=159) or placebo (n=156) for 10 weeks10.8 ± 9.6 (Silexan)
8.4 ± 8.9 (placebo)


In the Kasper (2010) study, the HAM-A score decrease was significant as of week 2 in the Silexan™ group (p<0.001). In the Woelke (2010) study, Silexan™ was as efficacious as low dose lorazepam 0.5 mg in adults with GAD without causing sedation or potential for abuse. In the Kasper (2014) trial, Silexan™ 160 and 80 mg daily were both superior to placebo in reducing the HAM-A total score (p<0.01). In Kasper (2015), Silexan™ 80 mg was once again superior to placebo (p<0.001). There was also a significant decrease in the Montgomery Asberg Depression Rating Scale (p<0.001) seen in this study when comparing Silexan to placebo.

Beyond being effective for reducing symptoms, Silexan™ is also extremely well tolerated. Adverse effects seen in clinical trials were uncommon and included nausea (5.2%), burping (3.9%) and dyspepsia (2.6%). It was shown to improve quality and duration of sleep by calming nervousness and increasing relaxation without causing sedation. 

The commercially available product in the US is called Lavela WS1265, which is a brand name for the Silexan™ formulation. You can find it on our fullscript store. It contains 80 mg of active ingredient, Lavandula angustifolia, and is taken as one softgel by mouth once or twice daily with a full glass of water. Lavela WS1265 has not been studied during pregnancy, lactation or in patients less than 12 years of age. This is not an FDA approved treatment for anxiety or other mood disorders, however it could be an option to discuss with you healthcare provider, to determine if it could be used for support and symptom relief.

References: 

  1. Baldwin DS, Montgomery SA, Nil R, Lader M. 2007. Discontinuation symptoms in depression and anxiety disorders. Int J Neuropsychopharmacol. 10:73–84.
  2. Haller H, Cramer H, Lauche R, Gass F, Dobos GJ. 2014. The prevalence and burden of subthreshold generalized anxiety disorder: a systematic review. BMC Psychiatry. 14:128–140. 
  3. Kasper S, Gastpar M, Müller WE, Volz HP, Möller HJ, Schläfke S. 2014. Lavender oil preparation Silexan is effective in generalized anxiety disorder: a randomized, double-blind comparison to placebo and paroxetine. Int J Neuropsychopharmacol. 17:859–869.
  4. Kasper S, Volz HP, Dienel A, Schläfke S. 2016. Efficacy of Silexan in mixed anxiety-depression: a randomized, placebo-controlled trial. Eur Neuropsychopharmacol. 26:331–340.
  5. Kessler RC, Demler O, Frank RG. 2005. Prevalence and treatment of mental disorders, 1990 to 2003. N Engl J Med. 352:2515–2523.
  6. Longo LP, Johnson B. 2000. Addiction: part I. Benzodiazepines-side effects, abuse risk and alternatives. Am Fam Physician. 61:2121–2128.
  7. Müller WE, Schuwald A, Nöldner M, Kasper S, Friedland K. 2015. Pharmacological basis of the therapeutic use of Silexan (Lasea). Psychopharmakotherapie. 22:3–14.
  8. Musazzi L, Racagni G, Popoli M. 2011. Stress, glucocorticoids and glutamate release: effects of antidepressant drugs. Neurochem Int. 59:138–149. 
  9. Kasper S, Gastpar M, Müller WE, Volz HP. 2010. Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of ‘subsyndromal’ anxiety disorder: a randomized, double-blind, placebo controlled trial. Int Clin Psychopharmacol. 25:277–287.
  10. Woelk H, Schläfke S. 2010. A multi-center, double-blind, randomized study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder. Phytomedicine. 17:94–99.

Preventing the Most Common Cause of Chronic Pain with Nutrition

The end of February is almost here, which means that our next Functional Medicine CE symposium is 1 week away! Dr. Frank Bodnar is rounding out his contribution to the blog with a great discussion on chronic pain and how we can use nutrition to improve inflammation. If you want to learn more and hear from Dr. Bodnar and our other speakers. Please make sure you sign up!

Dr. Hartzler

You’ve seen many patients walk into your clinic with a limp, antalgic posture or heard the grunts and groans of pain as they get in and out of their chairs. Thousands of people visit their local pharmacy for a remedy to ease their chronic ache and recurring nagging pain. There’s no doubt that inflammation is an underlying cause in the majority of your patient’s pain. We can help our patients break the cycle of grabbing a Tylenol off the shelf, only to return a few weeks later looking worse. At the end of the day, are your patients getting better?

You’re probably wondering where to start. You can get started by focusing on the most common cause of chronic pain, arthritis. And if we drill down into the term arthritis and look at a specific diagnosis, we see that osteoarthritis (OA) is the most common cause of chronic pain from a single disease standpoint. Not only is it the most common cause of chronic pain but also the leading cause of disability worldwide, affecting mobility, physical function and quality of life.1OA, or joint degeneration is the culprit behind the majority of your patients’ aches and pains.

Unfortunately, the problem isn’t going away any time soon. Epidemiological data shows that the US population continues to age, and by 2040, 1 in 5 people in the United States will be 65 or older—about equal in size to the cohort of those who are 18 years of age or younger. One in two adults aged 65 and older already have some form of arthritis, but nearly two-thirds of those with arthritis are under 65. By 2030, it is projected some form of arthritis will affect 67 million adults. Both osteoarthritis and inflammatory forms of arthritis are more common in women.

The problem of OA and joint degeneration isn’t new to any clinician but may be one of the most neglected in the functional medicine and pharmacy arenas because we assume patients may not seek us out as an option for such an uncomplicated condition. Most patients rely on self-care via anti-inflammatory and analgesic medication as a remedy. While this approach may get them through their day, we know this is symptom management and doesn’t really do anything to reduce inflammation over the long-term or prevent further joint degeneration. 

If we want to make a dent in the pain problem and prevent more invasive therapies in our aging population, we need to offer safe and effective treatments for the musculoskeletal system, which is the largest contributor to chronic pain.2 We’re going to cover the a few specific options that can make an immediate impact in breaking the vicious pain cycle your patients are stuck in. The aging process affects all aspects of a joint beyond just cartilage breakdown. The surrounding muscle begins to lose strength due to a decrease in muscle fibers and fiber size, and a reduction in muscle protein synthesis. Surrounding tendons also lose the ability to maintain water, lose tensile strength and elasticity and fibroblasts decrease glycosaminoglycan (GAG) production. Bones that surround primary weight bearing loads begin to decrease in strength due to less mineral content leading to more fragility, and the process of bone remodeling slows as well. Cartilage also loses its ability to decompress and hold water, along with a decreased ability to maintain joint lubrication through less hyaluronic acid production.3

When most clinicians think of OA, the first thing that comes to mind is a disease of “wear and tear.” We consider what we were taught during our training, which is to focus on the loss of joint space and a degradation of cartilage. While this isn’t completely inaccurate what we now know is that OA is much more involved than what we learned in pharmacy school even 10 years ago. A more accurate description of OA would be “whole joint failure,” just as loss of full function on the heart is diagnosed as heart failure and loss of full function of the kidney is diagnosed as renal failure. Whole joint failure involves not only the cartilage, but helps us take into consideration the underlying bone, synovial membrane, synovial fluid, tendons, muscles, nerves, nociceptor sensitivity and underlying metabolic factors (TIMP/MMP activity).4

Traditional drugs such as aspirin, ibuprofen, naproxen, celecoxib and steroids target primarily 5-LOX, COX-1, COX-2, PLA2 inflammatory pathways via oral medication or intraarticular injection to provide pain relief. Analgesics such as acetaminophen, narcotics and oxycodone may also provide symptomatic relief. However, this relief comes at a cost of more also blocking the body’s repair process and more cartilage loss than previously thought and higher risks than many are aware. Given the constraints of NSAIDs, especially in those with high cardiovascular risk, gastrointestinal and renal comorbidities, and constraints of acetaminophen in those with high risk of liver injury or at risk for multiple medication adverse reactions safer alternatives should be a primary consideration. In fact, a recent study at Boston University School of Medicine found accelerated arthritis and joint destruction can be the unintended result of intra-articular corticosteroid injections.5 Given the chronicity of OA we need alternatives that are safe and effective and can be taken long-term without the major side effects. 

Dietary Changes Can Reduce Inflammation and OA Progression

Diet has been shown to greatly influence the rate of joint degeneration, especially when obesity and insulin resistance are involved. Obesity is now a recognized generator of inflammation and adds to the mechanical pressure on a joint. The inflammatory and metabolic mechanisms as contributing factors to OA can no longer be ignored. A recent laboratory study testing synovial tissue from mice and individuals with type 2 diabetes suggested that the insulin resistance of type 2 diabetes may promote OA.6

Research also has shown that diet plays a key role in the regulation of inflammation, elevating C-reactive protein (CRP)7, and because there is a relationship between inflammation and the development and progression of OA, consuming diets shown to have anti-inflammatory effects may be an important step in preventing and halting the progression of the disease. In fact, even a single meal high in calories, fat, and highly palatable carbohydrates can induce an acute inflammatory response,8possibly contributing to flare-up and pain in OA.


The Standard American Diet is characterized by a high intake of processed meat, refined sugars, saturated fat, little fiber, and high arachidonic acid. This dietary pattern triggers the release of proinflammatory cytokines and reduce the production of anti-inflammatory cytokines.9Consuming trans fats from cakes, cookies, pie crusts, biscuits, margarine, and commercially fried foods have been shown to increase biomarkers of inflammation, specifically CRP and IL-6, especially in people who are overweight.10,11Focusing on whole unprocessed foods appears to be the most prudent strategy. One study using an inflammatory food index found that an anti-inflammatory diet consisting of foods rich in fish, fruits and vegetables, and olive oil was associated with lower levels of CRP.12

Specific Nutraceuticals to Mitigate Joint Degeneration and OA Progression

The other part of the equation is offering patients options that have been clinically proven to be effective for OA. Glucosamine sulfate and chondroitin sulfate are two nutraceuticals that are structural building blocks of the GAG polymers found in cartilage that play key roles in absorbing water, contributing to greater joint space, cartilage volume and give cartilage its ability to compress and decompress from forces and friction encountered throughout the day.13 Glucosamine sulfate and chondroitin sulfate at low-molecular weights (<17,000 kD) have also shown potent anti-inflammatory action by modulating the COX-1 and COX-2 pathways, and the ability to decrease cartilage degradation markers in human OA studies.

In a 2008 study published in the Journal of Orthopedics Traumatology, 104 patients diagnosed with OA of the hands, knee or hip were evaluated on pain scores (VAS), radiographic imaging and had biomarkers of cartilage degradation measured via urinary C-terminal crosslinking telopeptides of type II collagen (uCTX-II), and bone degradation measured via urinary C-terminal cross-linking telopeptides of type I collagen (uCTX-I). Scientists used these tests to evaluate the structural progression of OA and potential therapeutic efficacy of glucosamine sulfate and chondroitin sulfate. All measures were taken at baseline, 6 months and 1 year to gauge progression. After 6 months and 1-year they found the uCTX-I and uCTX-II markers were significantly lower in the glucosamine sulfate and chondroitin sulfategroups, along with VAS scores, compared to baseline measures. Radiographic evaluation showed a reduced progression in the hand OA group after 1 year. The authors concluded that glucosamine sulfate and chondroitin sulfatein combination can provide a protective effect in OA patients and shows evidence that they slow the progression of OA.14

Other notable clinical trials include a randomized, double-blind, placebo-controlled study called the GAIT Trial, which is the largest NIH funded study on joint health supplements to date. In the trial GS and CS where evaluated individually and in combination and compared to celecoxib for therapeutic efficacy.  In the study 1,583 OA patients were evaluated and it was found that those who received the most benefit in the moderate to severe pain group were given 1500 mg/day of glucosamine sulfate and 1200 mg/day of chondroitin sulfate. The study ran for 2-years with patients receiving a daily dose of glucosamine sulfate and chondroitin sulfate. Initial conclusions found no benefit for mild OA, however upon secondary analysis in the moderate to severe OA pain group glucosamine sulfate and chondroitin sulfatewas found to not only be effective for pain reduction but outperform celecoxib at the doses mentioned.15

In another randomized, double-blind, placebo-controlled study,called the MOSAIC Trial, 194 OA patients at five medical centers in Quebec were enrolled to gauge the efficacy of low-molecular weight chondroitin sulfatein comparison to celecoxib. Half of the patients received 1200 mg/day chondroitin sulfateand half received 200 mg/day of celecoxib over a 2-year period. Three MRIs, a clinical assessment, and WOMAC score were used to assess structural changes. These evaluation methods were done at the beginning, one year in and the end of the study. Loss of cartilage was a primary assessment. It was found that the chondroitin sulfatepatients had much slower progression of OA in comparison to celecoxib group. Both treatments were equal in pain reduction, maintaining function, joint stiffness, joint swelling and both improved symptoms by 50%. The authors noted the positive outcomes with chondroitin sulfate, as well as the fact that chondroitin sulfate doesn’t carry the risk of side effects as anti-inflammatory medications.16

Another randomized, double-blind, placebo-controlled study, called the CONCEPT Trial, compared celecoxib therapy to low-molecular weight chondroitin sulfate. Over 600 OA patients received either 800 mg/day of chondroitin sulfateor celecoxib. The study found 800 mg/day of low-molecular weight chondroitin sulfateto be superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in symptomatic knee OA patients. The authors concluded that this formulation of chondroitin sulfateshould be considered a first-line treatment in the medical management of knee OA.17

Finally, a study recently just published in Diabetes Carein January 2020. Found an association between glucosamine users and a lower incidents of Type 2 Diabetes (T2D). Since glucosamine is a glycosaminoglycan (GAG), the authors were looking to see if there was an association between glucosamine supplement use and an increase occurrence of diabetes. Previous scientific commentaries on glucosamine have hinted at glucosamine being avoided in the general population, and by diabetics, due to “possible” negative blood sugar consequences that would worsen insulin sensitivity and contribute to the onset or worsening of diabetes.

This study shows however that glucosamine may actually be protective against or hinder the onset of diabetes. The study analyzed over 400,000 individuals that had data input into the UK Biobank who were free of diabetes, cancer and cardiovascular disease at baseline (8 years prior). The authors then evaluated the association between glucosamine supplementation and risk of incident of Type 2 Diabetes (T2D). After adjusting for age, sex, BMI, race, lifestyle factors, history of disease, genetics and other supplement use they found that glucosamine was associated with significantly lower risk of T2D. The really exciting part was that that they found the strongest association in those that had the highest inflammatory levels of C-reactive protein (hs-CRP).18

How could a sugary protein possibly influence a metabolic disease like T2D? While most of us think about glucosamine as simply a “building block” in cartilage, pharmaceutical-grade glucosamine (low molecular weight) actually has a robust anti-inflammatory mechanism that is overlooked.19 This anti-inflammatory mechanism is most likely why glucosamine displayed such a strong association of less incidents of T2D in those with higher hs-CRP levels. Inflammation can affect everything from our cell’s ability to metabolize sugar efficiently to our pancreas’s ability to produce insulin, leading to hyperinsulinemia.

Glucosamine’s anti-inflammatory action also makes it ideal as a chondroprotective, helping cartilage cells, that grow and reproduce very slowly, stay alive longer and thrive by decreasing the inflammatory signaling that damages the cells directly and inhibits the activation of a class of cartilage degrading enzymes called matrix metallopeptidases (MMPs).19

Quality is the key when it comes to recommending a glucosamine sulfateor chondroitin sulfate product. Martel-Pelletier (2015) showed discrepancies of chondroitin quality and ranging levels of efficacy due to quality. It was found that low-molecular weight chondroitin sulfateis the only reliable form on the market, and larger chondroitin sulfate molecules could actually be pro-inflammatory in nature.20 Previous studies have also shown that large chondroitin sulfate molecules will not pass through the intestinal epithelium barrier, further contributing to the poor results of past trials with lower quality chondroitin sulfate. 

Glucosamine should be dosed at 1500 mg/day and chondroitin sulfate in combination at 800-1200 mg/day. Glucosamine does carry a precaution as a shellfish warning, and if pregnant or nursing it is recommended to consult a physician prior to use. Taking chondroitin in combination with glucosamine might increase the anticoagulant effects of warfarin (Coumadin) and increase the risk of bruising and bleeding as well. Generally both glucosamine sulfate and chondroitin sulfate are broken up to 2 or 3 daily doses and taken on an empty stomach.

References

  1. Neogi, T. (2013). The epidemiology and impact of pain in osteoarthritis. Osteoarthritis and Cartilage21(9), 1145-1153. 
  2. Castillo, S. (2016). The Burden of Musculoskeletal Diseases in the United States: Prevalence, Societal and Economic Cost (3rd Edition), United States Bone and Joint Initiative, NFP (USBJI) 
  3. Effects of Aging – OrthoInfo – AAOS. (2009), from https://orthoinfo.aaos.org/en/staying-healthy/effects-of-aging/
  4. O’Neill, T. and Felson, D. (2018). Mechanisms of Osteoarthritis (OA) Pain. Current Osteoporosis Reports,16(5), pp.611-616. 
  5. Andrew J. Kompel, Frank W. Roemer, Akira M. Murakami, Luis E. Diaz, Michel D. Crema, Ali Guermazi. Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Safe as We Thought? Radiology,2019; 190341 
  6. Hamada D, Maynard R, Schott E, et al. Suppressive effects of insulin on tumor necrosis factor-dependent early osteoarthritic changes associated with obesity and type 2 diabetes mellitus. Arthritis Rheumatol. 2016;68(6):1392-1402
  7. Giugliano D, Ceriello A, Esposito K. The effects of diet on inflammation: emphasis on the metabolic syndrome. J Am Coll Cardiol. 2006;48(4):677-685.
  8. Emerson, S., Kurti, S., Harms, C., Haub, M., Melgarejo, T., Logan, C., & Rosenkranz, S. (2017). Magnitude and Timing of the Postprandial Inflammatory Response to a High-Fat Meal in Healthy Adults: A Systematic Review. Advances In Nutrition: An International Review Journal8(2), 213-225. 
  9. Clinton CM, O’Brien S, Law J, Renier CM, Wendt MR. Whole-foods, plant-based diet alleviates the symptoms of osteoarthritis. Arthritis. 2015;2015:708152.
  10. Mozaffarian D, Pischon T, Hankinson SE, et al. Dietary intake of trans fatty acids and systemic inflammation in women. Am J Clin Nutr. 2004;79(4):606-612.
  11. Lopez-Garcia E, Schulze MB, Meigs JB, et al. Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction. J Nutr. 2005;135(3):562-566.
  12. Cavicchia PP, Steck SE, Hurley TG, et al. A new dietary inflammatory index predicts interval changes in serum high-sensitivity C-reactive protein. J Nutr. 2009;139(12):2365-2372.
  13. Tang, Y., Cui, Y., De Agostini, A., & Zhang, L. (2019). Biological mechanisms of glycan- and glycosaminoglycan-based nutraceuticals. Progress In Molecular Biology and Translational Science, 445-469. 
  14. Scarpellini, M., Lurati, A., Vignati, G. et al.Biomarkers, type II collagen, glucosamine and chondroitin sulfate in osteoarthritis follow-up: the “Magenta osteoarthritis study”. J Orthopaed Traumatol9, 81–87 (2008).
  15. Clegg, D., Reda, D., Harris, C., Klein, M., O’Dell, J., & Hooper, M. et al. (2006). Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis. New England Journal Of Medicine354(8), 795-808. 
  16. Pelletier, J., Raynauld, J., Beaulieu, A., Bessette, L., Morin, F., & de Brum-Fernandes, A. et al. (2016). Chondroitin sulfate efficacy versus celecoxib on knee osteoarthritis structural changes using magnetic resonance imaging: a 2-year multicentre exploratory study. Arthritis Research & Therapy18(1). 
  17. Reginster J, Dudler J, Blicharski T, et al. Pharmaceutical-grade Chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT)Annals of the Rheumatic Diseases2017;76:1537-1543.
  18. Ma, H., Li, X., Zhou, T., Sun, D., Liang, Z., & Li, Y. et al. (2020). Glucosamine Use, Inflammation, and Genetic Susceptibility, and Incidence of Type 2 Diabetes: A Prospective Study in UK Biobank. Diabetes Care, dc191836. 
  19. Jerosch, J. (2011). Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids. International Journal Of Rheumatology2011, 1-17.
  20. Martel-Pelletier J, Farran A, Montell E, Vergés J, Pelletier JP. Discrepancies in composition and biological effects of different formulations of chondroitin sulfate. Molecules. 2015;20(3):4277–4289. Published 2015 Mar 6.

Sub-Acute Pain and Healing Support with Nutraceutical and Lifestyle Recommendations

Pain is the number #1 reason why people enter the system. Pharmacists get questions about pain management strategies on a daily basis regardless of their setting. This is one of the reasons we choose pain and inflammation to be our next symposium topic for FxMedCE.com. We want more providers to understand the types of pain and how to help our patients. I hope you enjoy another great blog post from Dr. Frank Bodnar, DC. He is will be one of the speakers, make sure you sign up to hear from him as well as others who have spoken across the globe. Continuing Education Credit is available for Pharmacists and Certified Nutrition Specialists (CNS). Others are welcome to join!

Dr. Hartzler

One of the most overlooked phases of pain and healing is the sub-acute phase. There’s some uncertainty about how to best approach sub-acute pain from a pharmacist’s perspective since it’s not really acute, and it’s not chronic. Often this puts patients in a “no-man’s-land” of self-management with no clear direction of where we want them to go and why, so patients do what they’ve always done. They go back to the medicine cabinet for another pain reliever. 

Helping patients navigate the middle ground of pain and healing presents a fantastic opportunity where pharmacists can help prevent the cycle of pill dependency for pain. This shift allows the body to do the healing. After all the injury didn’t occur by a deficiency in ibuprofen or acetaminophen and won’t fully support the body’s middle phase of structural healing if the cycle continues. The cycle of dependency may lead the patient down a road of more potent like a cortisone injection or even a prescription opioid. Pharmacists can alter this trajectory.

The majority of the time the sub-acute phase of care is treated with the exact same approach as an acute phase, despite there being clear physiologic differences. It’s understandable that there is some overlap between the acute and sub-acute phases and major guidelines may overlook the need for a different approach.  

Traditionally the American College of Physiciansrecommends a number of both pharmaceutical and non-pharmaceutical options for sub-acute low back pain,1and within the realm of therapies available there are a number of other options available as well:

  • Cryotherapy
  • Heat
  • Electrotherapy
  • Ultrasound
  • Low level laser
  • TENS Machine
  • Electrical Stimulation
  • Spinal manipulation
  • Massage
  • Acupuncture
  • Dry needling
  • Kinesio taping
  • Instrument assisted soft tissue mobilization
  • Exercise rehabilitation
  • Anti-inflammatory drugs
  • Topical analgesic 
  • Skeletal muscle relaxants

While all of the therapies listed above are traditionally appropriate in the management of sub-acute pain and healing, they are primarily focused on symptom management and leave out nutrition completely. Healing is a complex process that requires proper key nutrients for inflammatory control, new tissue formation, and tissue remodeling to occur within a specific time frame to get back to optimal function. Simply reaching for the bottle in the medicine cabinet isn’t sufficient.

In some cases, all three phases of the healing process may take 12-18 months to be fully completed depending on the tissue type and injury severity.2Managing patient expectations is an essential part of pain management. If patients understand the phases of healing and goal of therapies at each phase, you can begin to provide the roadmap to a pain-free future.

During sub-acute pain the focus of the body with many injuries is connective tissue repair and rebuilding structural integrity. Connective tissue regeneration and repair begins with fibroblasts producing type I and type III collagen fibers, which are randomly orientated, immature, and weak in comparison to the well-organized, dense fibers of type I collagen. Depending on the structure, type II collagen and extracellular matrix material like hyaluronic acid and other polysaccharides help to aggregate, organize and allow proper structure movement to occur.3

The remodeling phase requires gradual collagen and connective tissue cross-linking, which is dependent on the vital cofactor vitamin C. Vitamin C activates hydroxylases, allowing proper collagen fiber assembly and helical structure formation to occur.4If connective tissue alignment and aggregation is limited, collagen fiber orientation remains disorganized and overall function remains limited. This area will likely be a site of reinjury, and vitamin C plays a key role in preventing this.5

Clinical studies on nutraceuticals as bioactive collagen peptides, type I collagen, hyaluronic acid and essential cofactors for collagen formation have shown they not only reduce rehabilitation time, but also endogenously stimulate chondrocytes, fibroblasts and synovial cells to produce their native raw materials. In addition, these studies also show reduced cytokines such as IL-1β, which stimulate a class of connective tissue-degrading enzymes called matrix metalloproteinases (MMPs) .6-8Structural support and inflammatory support at the cellular level are essential to reducing the risk of re-injury in all connective tissues.

The best nutraceuticals to offer patients during a sub-acute pain episode is a combination of high-quality type I and type II collagen peptides, hyaluronic acid, mucopolysaccharides, vitamin C and magnesium. These nutrients cover over 90% of the connective tissue in the body and undoubtedly would enhance he sub-acute phase of healing and repair. Not only do they support the connective tissue cells, the process of protein synthesis and collagen cross-linking but they also have clinical studies with positive clinical outcomes. Of course, sometimes simply offering an alternative to a muscle-relaxer may be appropriate as well. 

Tendinopathies are largely an overuse injury and represent a good example of what will also support connective tissue regeneration and repair during a sub-acute phase of pain and healing. A 2014 study out of Barcelona and Madrid, Spain treated tendinopathy patients at multiple hospitals and sports rehabilitation clinics around the area with high-quality type I collagen peptide that also contained vitamin C, magnesium and naturally occurring mucopolysaccharides. A total of 98 patients with Achilles tendinitis, patellar tendinitis and lateral epicondylitis received a dose of 435 mg mucopolysaccharides, 75 mg type I collagen peptides and 60 mg of vitamin C for 90 days. Clinical symptoms improved by 38% (during activity and rest) on average and a decrease in tendon thickness was observed upon ultrasound evaluation – indicating less inflammation and tendon hypertrophy.9

There are valid options available that get results and support the body during the healing process and your patients should be aware. Below are some key evidence-based sub-acute pain and healing nutraceuticals:

NutrientDoseMechanism
GABA10250mg/day for 30 days Primary inhibitory neurotransmitter of the brain promotes relaxation and inhibits over-firing that results in muscle spasm and pain. Also shown clinically to improve sleep, promote alpha brain waves and improve REM sleep cycle. 
Glycine11225mg/day for 30 days Primary inhibitory neurotransmitter of the spinal cord promotes relaxation and inhibits over-firing that results in muscle spasm and pain, as well as promoting sleep quality. 
Cramp Bark12200mg/day for 30 days Anti-inflammatory and promotes smooth muscle relaxing effects. Not only effective for muscle spasms of the neck and low back but has shown effectiveness with menstrual cramping as well. 
Dong Quai Root Extract12150mg/day for 30 days Anti-inflammatory and promotes smooth muscle relaxing effects. Not only effective for muscle spasms of the neck and low back but has shown effectiveness with menstrual cramping as well.
Type I collagen peptides with mucopolysaccharides13-16500 mg/day for 90-180 days Type I collagen building block and stimulates tenocytes and fibroblasts to produce type I collagen in tendons, ligaments and skin. Clinical studies have shown improvement in medial and lateral epicondylitis, Achilles tendinitis and patellar tendinitis. 
Type II collagen peptides17-195 g/day for 90-180 days Type II collagen building block and stimulates chondrocytes and to produce type II collagen in cartilage and stimulates chondrocytes to endogenously produce more type II collagen.
Hyaluronic acid20-2240-80 mg/day for 90-180 days Increases hyaluronic acid concentration in synovial fluid and stimulates synoviocytes to increase HA production for joint and connective tissue hydration and lubrication. Clinical studies have shown improvements in pain scores, mobility and decreased synovitis in OA patients. 
Vitamin C23100 mg/day for 90-180 days Maximizes hydroxylases for optimal collagen and hyaluronic acid production and provides antioxidant support to optimize connective tissue healing, decreases histamine production, modulates immune response and new studies show potential reduction of pain.
Magnesium24135 mg/day for 90-180 days Co-factor for over 350 enzymes in the body, decreases chronic pain signaling via NMDA receptors, and shown to decrease pain in low back and headache patients. 

Supporting the body’s natural healing process is paramount and in some patients, this means digging a little deeper into lifestyle factors that can limit this process. The final missing variables in the sub-acute pain and healing equation is addressing the patient’s lifestyle by doing a quick evaluation of their stress levels and sleep quality. We know that the stress response can delay healing, and sleep is the primary time when the body is in repair mode. In a clinical trial published in Psychoneuroendocrinology, scientists looked at participants’ cortisol levels, perceived stress and health behaviors and how all of the factors affected wound healing. What they found was that cortisol had a considerable influence on wound healing independent of participants’ health behaviors. 25 

Multiple studies have also looked at sleep quality on healing, showing that poor sleep elevates cortisol, increases fatigue and errors made at work and results in worse patient health outcomes.26,27In one study the health of patients recovering in hospitals revealed that sleep was crucial for healing and survival of critically ill patients and greatly influenced the outcomes of patients suffering from a myriad of diseases. In fact, less sleep disruptions in critically ill patients showed much better outcomes in the literature compared to those with constant disruptions from health care practitioners during their recovery time.27       

Changing the patient’s perspective on pain and implementing easy nutrient and lifestyle recommendations doesn’t have to be a complicated process. There are cortisol tests and sleep study methods available, but many patients want an immediate solution that will allow them to improve immediately. Simply having a conversation about how to best serve a patient will reveal the best nutrient offering and implementing a 5-minute stress questionnaire can reveal how stress and sleep may be limiting the sub-acute healing process. Start by simply engaging patients and offering the best recommendation for their specific situation and you’ll put them on the path to letting he body do what it does best.

References:

  1. Qaseem, A., Wilt, T., McLean, R., & Forciea, M. (2017). Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline from the American College of Physicians. Annals of Internal Medicine166(7), 514. 
  2. Reichert, W., Stroncek, J., & Reichert, W. (2008). Indwelling Neural Implants: Strategies for Contending With the in Vivo Environment (Frontiers in neuroengineering)(Chapter 1: Overview of Wound Healing in Different Tissue Types). Boca Raton, FL: CRC Press.
  3. Broughton, G., 2nd, J. E. Janis, et al. (2006). “The basic science of wound healing.” Plast Reconstr Surg 117(7 Suppl): 12S-34S
  4. DePhillipo, N. N., Aman, Z. S., Kennedy, M. I., Begley, J. P., Moatshe, G., & LaPrade, R. F. (2018). Efficacy of Vitamin C Supplementation on Collagen Synthesis and Oxidative Stress After Musculoskeletal Injuries: A Systematic Review. Orthopaedic journal of sports medicine6(10), 2325967118804544. 
  5. Ömeroğlu, S., Peker, T., Türközkan, N., & Ömeroğlu, H. (2008). High-dose vitamin C supplementation accelerates the Achilles tendon healing in healthy rats. Archives of Orthopaedic And Trauma Surgery129(2), 281-286. 
  6. Iwai K, Hasegawa T, Taguchi Y, Morimatsu F, Sato K, Nakamura Y, Higashi A, Kido Y, Nakabo Y, Ohtsuki K, 2005. Identification of food-derived collagen peptides in human blood after oral ingestion of gelatin hydrolysates. J Agric Food Chem, 53, 6531-6536.
  7. Oesser S, Adam M, Babel W, Seifert J, 1999. Oral administration of (14) C labeled gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL). JNutr, 129, 1891-1895.
  8. P. Lundquist, P. Artursson . Oral Absorption of peptides and nanoparticles across the human intestine. Advanced Drug Delivery Reviews106 (2016) 256–276
  9. Arquer, A., et al. (2014). The efficacy and safety of oral mucopolysaccharide, type I collagen and vitamin C treatment in tendinopathy patients.
  10. Yoto, A., et al. (2011). Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids, 43(3), pp.1331-1337. 
  11. Kawai, N., et al. (2014). The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus. Neuropsychopharmacology, 40(6), pp.1405-1416. 
  12. Nicholson, J. A., Darby, T. D., and Jarboe, C. H. Viopudial, a hypotensive and smooth muscle antispasmodic from Viburnum opulus. Proc.Soc. Exp Biol.Med. 1972;140(2):457-461) 
  13. Schunk M and Oesser S. Specific collagen peptides benefit the biosynthesis of matrix molecules of tendons and ligaments. J Int Soc Sports Nutr. 2013; 108. 
  14. Shakibaei M, Buhrmann C, Mobasheri A. Anti-inflammatory and anti-catabolic effects of TENDOACTIVE® on human tenocytes in vitro. Histol Histopathol. 2011 Sep;26(9):1173-85.
  15. Balius et al. A Randomized, Placebo-Controlled Study to Evaluate Efficacy and Safety of A Dietary Supplement Containing Mucopolysaccharides, Collagen Type I and Vitamin C for Management of Different Tendinopathies. Ann Theum Dis. 2014;73, Suppl. 2:299- 30018. 
  16. Proksch E, Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis. Skin Pharmacol Physiol. 2014;27(3):113-9. doi: 10.1159/000355523. 
  17. McAlindon TE, Nuite M, Krishnan N, Ruthazer R, et al. Changes in knee osteoarthritis cartilage detected by delayed gadolinium enhanced magnetic resonance imaging following treatment with collagen hydrolysate: a pilot randomized controlled trial. Osteoarthritis and Cartilage19 (2011) 399e405 7.
  18. Zuckley L, Angelopoulou K, Carpenter MR: Collagen hydrolysate improves joint function in adults with mild symptoms of osteoarthritis of the knee. Medicine and Science in Sports and Exercise 2004, 36 (Supplement), 153 – 155. 
  19. Clark KL, Sebastianelli W, Flechsenhar KR, Aukermann DF, Meza F, Millard RL, Deitch JR, Sherbondy PS, Albert A: Long-term use of collagen hydrolysate as a nutritional supplement in athletes with activity-related joint pain. Curr Med Res Opin. 2008 May;24(5):1485-96.6.
  20. Torrent A, Ruhí R, Theodosakis J, et al. Comparative efficacy of IB0004, extracted hyaluronic acid (HA) and fermented HA on the synthesis of endogenous HA by human synoviocytes. Osteoarthritis Cartilage. 2009;17(Suppl 1):S278-79. – 10x HA secretion9. 
  21. Torrent A, Ruhí R, Martínez C, et al. Anti-inflammatoryactivity and absorption of a natural rooster comb extract. Osteoarthritis and Cartilage. 2010 Oct;18(Suppl 2):S246-47. 
  22. Möller I, Martinez-Puig D, Chetrit C. Oral administration of a natural extract rich in hyaluronic acid for the treatment of knee OA with synovitis: a retrospective cohort study. Clinical Nutrition Supplements2009;4(2):171-17211
  23. Carr, A., & McCall, C. (2017). The role of vitamin C in the treatment of pain: new insights. Journal of Translational Medicine, 15(1). doi: 10.1186/s12967-017-1179-7
  24. Na HS, Ryu JH, Do SH. The role of magnesium in pain. In: Vink R, Nechifor M, editors. Magnesium in the Central Nervous System [Internet]. Adelaide (AU): University of Adelaide Press; 2011.
  25. Ebrecht, M., Hextall, J., Kirtley, L., Taylor, A., Dyson, M., & Weinman, J. (2004). Perceived stress and cortisol levels predict speed of wound healing in healthy male adults. Psychoneuroendocrinology,29(6), 798-809. 
  26. Niu, S., Chung, M., Chen, C., Hegney, D., O’Brien, A., & Chou, K. (2011). The Effect of Shift Rotation on Employee Cortisol Profile, Sleep Quality, Fatigue, and Attention Level. Journal of Nursing Research19(1), 68-81. 
  27. Tembo, A., & Parker, V. (2009). Factors that impact on sleep in intensive care patients. Intensive and Critical Care Nursing25(6), 314-322. 

3 Ways Nutrition Can Help with Acute Pain and Inflammation

I know it’s been awhile since I’ve posted here. One reason is I’ve been busy with the launch of FunctionalMedicineCE.com a few months ago. We are hosting our second virtual symposium in a few weeks on February 29th. Dr. Frank Bodnar, DC is one of our speakers and he wrote this great post about ways we can use nutrition in inflammation and addressing pain. I hope this is beneficial to both pharmacists and patients out there as we journey on to healing together.

Dr. Hartzler

Pharmacists play a crucial role in treating acute pain and inflammation. If patients don’t head to the emergency room or urgent care center, their local pharmacy is certainly the next destination. The advantage as a pharmacist is that managing acute conditions doesn’t have to require a lengthy consultation or a complex workup. While providing clarity on the best over-the-counter analgesic to help manage acute symptoms is crucial, the value pharmacists can provide extends well beyond the normal transaction. You observe not only the grimaces, body language and postures of different pain issues but can offer an effective nutraceutical solution that targets the same biochemical pathway as traditional pharmaceuticals that a patient would otherwise never hear about.   

It’s fair to say that most pharmacists want the best for their patients’ health and are a highly trusted player on the patient’s health care team. Offering nutritional recommendations to a patient’s self-care acute pain strategy doesn’t have to be complicated. The most common traditional treatments of acute pain and inflammation reinforce blocking inflammation as the primary strategy. Nutraceuticals also have literature that show NFkB, PLA2, 5-LOX, COX-2 and COX-1 pathway modulation and clinical efficacy with a variety of inflammatory conditions.1-5

No clinician would disagree that controlling inflammation, reducing pain and improving a patient’s function as quickly as possible are good, ethical strategies. A patient-centered pharmacist understands not only the side effects and nutrient depletions but the best long-term healing mechanisms that should be considered as well. The value is more complete healing, less future pain and a satisfied patient that will let others know about their experience and your expertise.

Acute pain and inflammation can last anywhere from 1-3 days, with cardinal signs of heat, redness, swelling, pain and loss of function lingering a bit longer. Acute inflammation is driven by the body’s immune system responding to tissue injury and plays a key role in stimulating the pain signaling from the peripheral tissue. Local chemokines and pain hormones signal the initiation of vasodilation, white blood cell infiltration and clotting factors and immunoglobulins, soon followed by tissue regenerating cells such as fibroblasts. Biochemically we see acute-phase proteins such as C-reactive protein (CRP), cytokines, growth factors, eicosanoids, adhesion molecules and matrix metalloproteinases elevated.6If inflammation and free radical damage continues tissue injury and fibrosis can occur.7

The body does a great job of stopping the damage, cleaning the injured area and quickly beginning the repair process, and we want to support these processes as much as possible rather than just focusing on their inhibition. Emerging studies are showing that blocking the inflammatory response may result in delayed healing in bone in the short-term and possibly other connective tissues over the long run, possibly resulting in tissue that is at risk for future irritation and injury.8,9 Diet and supplementation have been shown to support healing and inflammatory mechanisms10 and offer a key strategy beyond resting, icing, compressing and elevating (RICE) an injury. 

During acute pain and inflammation there are three primary nutritional recommendations that can be incorporated to enhance your patient’s outcomes.

  1. 14-Day Anti-Inflammatory Diet: even with trauma, infection and surgery implementing a diet that focuses on fresh fruits, vegetables, nuts, seeds, anti-inflammatory fats and high-quality sources of protein can enhance the acute healing process and help reduce the potential for pain and inflammation to be further perpetuated. Omega-3 fatty acids, monounsaturated fatty acids, phytonutrients that are packed with antioxidants and natural anti-inflammatory compounds and lean proteins all play pivotal roles in reducing the inflammatory response and aiding in the healing process. The Anti-Inflammatory diet template and should include high amounts of nutrient dense foods:
    1. Protein: Fish, lean meat (beef, chicken), omega-3 eggs, high-quality rice and pea protein powders
    1. Green leafy and cruciferous vegetables: kale, collard greens, spinach, red cabbage, beets, watercress, romaine lettuce, cauliflower, broccoli, artichokes and brussels sprouts
    1. Healthy fats: avocado, olive oil, coconut oil and see list of nuts and seeds
    1. Fruits (high in antioxidants and fiber): strawberries, blueberries, blackberries, raspberries, cranberries, red or purple grapes, kiwi, pineapple, grapefruit, apples, pomegranate, mango, oranges, apples, papaya and cherries
    1. Tubers and others: sweet potatoes, carrots, acorn squash and butternut squash, zucchini, beans, olives, tomatoes, peppers, onions and garlic
    1. Nuts and seeds: almonds, pistachios, walnuts, cashews, pecans, macadamia, brazil nuts, and hazelnuts 
  • Whole Turmeric Matrix Supplementation: 500 – 1,000 mg/day for 14 days

The phytochemical analysis of turmeric has revealed that there are 200-plus bioactive molecules present in the natural matrix of turmeric that contribute to its health benefits. The main constituents are the curcuminoids, which include curcumin, demethoxy curcumin and bis-demethoxy curcumin. In addition to this, the non-curcuminoid components like turmerin, turmerones, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone11-14all showing the ability to reduce pain and inflammation separate from curcumin.15,16,19-23The broad-spectrum of bioactives mechanistically go above and beyond the primary targets traditional therapies (COX-2, 5-LOX and TNF-α). Whole turmeric root modulates NFkB and pretty much every downstream cytokine and growth factor resulting in less COX-2 activation, MAPK p38 pathway modulation and iNOS expression,12,13which for a patient means less pain, less inflammation and less swelling. Recently, scientists have discovered that the microbiome metabolizes these bioactives and they enhance the anti-inflammatory signaling capacity of turmeric’s bioactives. Studies show turmeric’s bioactives increase microbiome diversity, inhibit and protect the body from LPS-induced inflammation,17fortifying enterocyte tight junctions and increasing afferent vagus nerve signaling.18These broad mechanisms provide a range of benefits that truly match the mechanistic needs of arthritic joints beyond a wear and tear, and local inflammatory approach. 

Multiple double-blind, placebo-controlled clinical trials of osteoarthritis and rheumatoid arthritis patients have shown not only a decrease in pain, increase in joint function, and improved inflammatory and autoimmune biomarkers, but have also outperformed NSAIDs in head-to-head trials.15,19-23

  • Flavonoid and Bromelain Supplementation Recommendation: Bromelain 240 mg (576 GDU)/day, Quercetin Dihydrate 240 mg/day, and Rutin 50 mg/day for 14 days. 

Bromelain is a mixture of enzymes found in the stem of the pineapple (Ananas comosus) that exhibit proteolytic characteristics. Bromelain also supports the chondrocyte’s normal cell cycle via the p53, NFkB and Bcl-2 pathways, and balances IL-1B, IL-6, INF-y, TNF-α cytokines via PGE-2 and COX-2 activity during normal local immune responses. Locally bromelain modulates plasma kinins and fibrin/fibrinogen proteins via MMP, VEGF, bFGF, and EGF activity which all contribute to normal vascular and blood supply to connective tissue and prevent excess fibrosis.24

  • A randomized, double-blinded, placebo-controlled study done on performed on 176 boxers found that bromelain supported exercise recovery with notable improvements in bruising on the face and orbits, lips, ears, chest and arms in as little as four days compared to placebo.22
  • A 2017 randomized clinical study published in Rheumatology and Orthopedic Medicine, compared standard medical therapies to proteolytic enzyme therapy in 74 patients with acute joint pain. Patients were evaluated with joint outcome measures, VAS score, hs-CRP, ESR, and liver (ALT, AST) and kidney (creatinine) markers. The results showed that bromelain lowered hs-CRP, ESR improved joint function scores and while keeping normal liver and kidney function and showing no damage the gastric mucosa.23

Quercetin is a powerful antioxidant flavonoid in plants including oak trees, onions and tea. Cell studies show quercetin inhibits COXs and LOX enzymes which produce prostaglandins and leukotrienes; reduces inflammatory pain by inhibiting oxidative stress and cytokine production; LPS-induced TNF-a, IL-8, IL-1a release; prevents mast cell release of histamine and inhibits adhesion molecules such as VCAM-1.25Similar to turmeric quercetin has also been shown to support barrier function in the intestines,26,27modulate NFkB, MAP kinases and inhibit hyaluronidases and MMPs, which are degradatory connective tissue enzymes.25

  • A 2019 meta-analysis combined the data of six randomized controlled trials consistent improvements in the acute-phase biomarker, hs-CRP, and while other cytokines such as IL-6 and TNF-a were found to be decreased in individual studies a statistical significance wasn’t reached in the combined data. Overall the authors concluded that quercetin supplementation for pain and inflammation is a promising therapeutic.28

Rutin is a flavonol found abundantly in plants such as apples, tea, buckwheat and passionflower. Rutin supports connective tissue health by inhibiting the enzymes hyaluronidase, collagenase, LOX and COXs, which all contribute to the degradation of connective tissue, and exhibits neuroprotective, analgesic, antiarthritic, broad-spectrum anti-inflammatory support and speeds wound healing in vitro.29

  • A meta-analysis of six randomized controlled trials published in the Journal of Pain Research, compared 270 knee patients who received a combination of rutin and bromelain (OEC) to 266 standard patients who received standard medical therapy. The authors found OEC to be comparable for efficacy while tolerable and safe.30

References:

  1. Al-Okbi, S. (2012). Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis. Toxicology and Industrial Health30(8), 738-749. 
  2. Sevda Inan (2019). The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress, Nutraceuticals – Past, Present and Future, María Chávarri Hueda, IntechOpen, DOI: 10.5772/intechopen.83797.
  3. Gupta, S., Prasad, S., & Aggarwal, B. (2016). Anti-inflammatory Nutraceuticals and Chronic Diseases(1st ed., pp. 1-25). Cham: Springer International Publishing.
  4. Al-Okbi, S. (2012). Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis. Toxicology and Industrial Health30(8), 738-749.
  5. Ravalli S, Szychlinska MA, Leonardi RM, Musumeci G. Recently highlighted nutraceuticals for preventive management of osteoarthritis. World J Orthop 2018; 9(11): 255-261
  6. Jain, S., Gautam, V., & Naseem, S. (2011). Acute-phase proteins: As diagnostic tool. Journal of pharmacy & bioallied sciences3(1), 118–127. doi:10.4103/0975-7406.76489
  7. Edwards, S. (2020). Pathophysiology of Inflammation – Pharmacology – Manual. Retrieved 10 Jan. 2020, from https://www.merckvetmanual.com/pharmacology/anti-inflammatory-agents/pathophysiology-of-inflammation
  8. Su, B., & O’Connor, J. (2013). NSAID therapy effects on healing of bone, tendon, and the enthesis. Journal of Applied Physiology115(6), 892-899. doi: 10.1152/japplphysiol.00053.2013 
  9. Serra, M., et al. (2017). From Inflammation to Current and Alternative Therapies Involved in Wound Healing. International Journal of Inflammation2017, 1-17. doi: 10.1155/2017/3406215
  10. Seaman, D. (2017). An Anti-inflammatory Diet for Pain Patients. Retrieved 10 February 2020, from https://www.practicalpainmanagement.com/treatments/complementary/anti-inflammatory-diet-pain-patients
  11. Suzuki, M and T Nakamura. “Elucidation of Anti-Allergic Activities of Curcumin-Related Compounds with a Special Reference to their .” Biol. Pharm(2005): 1438-1443 
  12. Panahi, Y., Darvishi, B., Ghanei, M., Jowzi, N., Beiraghdar, F., & Varnamkhasti, B. (2016). Molecular mechanisms of curcumins suppressing effects on tumorigenesis, angiogenesis and metastasis, focusing on NF-κB pathway. Cytokine & Growth Factor Reviews, 28, 21-29. 
  13. Camacho-Barquero, L., Villegas, I., Sánchez-Calvo, J., Talero, E., Sánchez-Fidalgo, S., Motilva, V., & Alarcón de la Lastra, C. (2007). Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. International Immunopharmacology, 7(3), 333-342. 
  14. Kumar S, Ahuja V, Sankar MJ, Kumar A, Moss AC. Curcumin for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev(2012 Oct 17;10:CD008424.
  15. Daily, J and Mini, Park, S Yang. “Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trial. Journal of Medicine Food(2016): 717-729
  16. Amalraj, A, K Varma and Joby Jacob. “A Randomized, Double Blind, Placebo-Controlled, Two Dose, Three Arm, and Parallel-Group Study.” Journal of Medicinal Food(2017): 1022-1030
  17. Peterson, C., Vaughn, A., Sharma, V., Chopra, D., Mills, P., Peterson, S., & Sivamani, R. (2018). Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study. Journal of Evidence-Based Integrative Medicine, 23, 2515690X1879072. doi: 10.1177/2515690×18790725
  18. Wang, J., Ghosh, S., & Ghosh, S. (2017). Curcumin improves intestinal barrier function: modulation of intracellular signaling, and organization of tight junctions. American Journal of Physiology-Cell Physiology, 312(4), C438-C445. 
  19. ZHAO, F., GONG, Y., HU, Y., LU, M., WANG, J., & DONG, J. et al. (2014). Curcumin and its major metabolites inhibit the inflammatory response induced by lipopolysaccharide: Translocation of nuclear factor-κB as potential target. Molecular Medicine Reports, 11(4), 3087-3093. doi: 10.3892/mmr.2014.3079
  20. Rathnavelu, V., Alitheen, N., Sohila, S., Kanagesan, S., & Ramesh, R. (2016). Potential role of bromelain in clinical and therapeutic applications. Biomedical Reports, 5(3), 283-288. 
  21. Pavan, R., Jain, S., Shraddha, & Kumar, A. (2012). Properties and Therapeutic Application of Bromelain: A Review. Biotechnology Research International, 2012, 1-6. 
  22. Blonstein JL, Practitioner, Control of swelling in boxing injuries. 01 Aug 1969, 203(214):206].
  23. LS, M., M, et al. (2017). Efficacy of a combination of fixed doses of serratiopeptidases, bromelain and methylsulfonylmethane in inflammatory joint diseases. Rheumatology And Orthopedic Medicine, 2(3).
  24. Pavan, R., Jain, S., Shraddha, & Kumar, A. (2012). Properties and Therapeutic Application of Bromelain: A Review. Biotechnology Research International, 2012, 1-6.
  25. Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M., & Wang, S. et al. (2016). Quercetin, Inflammation and Immunity. Nutrients,8(3), 167.
  26. Lee, B., Moon, K., & Kim, C. (2018). Tight Junction in the Intestinal Epithelium: Its Association with Diseases and Regulation by Phytochemicals. Journal of Immunology Research, 2018, 1-11.
  27. Amasheh M, et al. Quercetin enhances epithelial barrier function and increases claudin-4 expression in Caco-2 cells. J Nutr2008 Jun;138(6):1067-73.
  28. Ou, Q., Zheng, Z., Zhao, Y., & Lin, W. (2019). Impact of quercetin on systemic levels of inflammation: a meta-analysis of randomised controlled human trials. International Journal Of Food Sciences And Nutrition, 1-12.
  29. Ganeshpurkar, A., & Saluja, A. (2017). The Pharmacological Potential of Rutin. Saudi Pharmaceutical Journal, 25(2), 149-164.
  30. Ueberall, M., Mueller-Schwefe, G., Wigand, R., & Essner, U. (2016). Efficacy, tolerability, and safety of an oral enzyme combination vs diclofenac in osteoarthritis of the knee: results of an individual patient-level pooled reanalysis of data from six randomized controlled trials. Journal Of Pain Research, (9), 941-961.

Holiday Shopping Ideas & Cyber Monday

I’m sure you are getting a ton of emails today with awesome deals. I just thought I’d share some of my favorites! Some of these are affiliate links where I do recieve a small commission that allows me to keep adding content to this site!

Amazon Items:

Other Ideas & Deals!

I love making gift baskets like a “spa basket” or a healthy eats basket. One year I included one of the cook books above and make some of the pancake mixes in a cute jars ready to go for my sister-in-law.

  • Essential Oil gifts can be great. Cyber Monday deals are live on over on my Young Living Store. If just shopping Retail (hit “no thanks” under the become a member) But consider a starter kit as a great way to learn about the oils and split some up for gifts. Pinterest can open up the world of gift ideas to create with essential oils. Hand scrubs are super easy with oils and salt in a cute mason jar. I also love snagging chapstick sets to split, plus facial and bath products to create my gift baskets. Orange Blossom Face Wash, ART Renewal Serum, and the ART Cream Masque are my favs!
  • Young Living also has the best clean make-up called Savvy Minerals. Eyeshadow pallets make great gifts as well as make-up brushes.
  • Vital Proteins also has a great sale today. Free 5 oz can of collagen peptides with a $50 order. If you missed it, check out my post on collagen’s benefits on the skin. Lots of options for gift baskets, including the coffee creamers with a bag of your favorite grounds.
  • We also have a sale on my Fullscript store today 15% off! Everyone needs some Vitamin C or Viracid in their stocking right? You can also make gift baskets with Vitamin D, Zinc lozenges, Thieves hand sanitizer, Vitamin C, etc. Perfect teacher gifts!
  • Myobuddy Massager is a great gift for you or your loved ones. This keeps me pain free between OMT and Chiropractic visits! Use the code CYBER at checkout for $50 off Pro 2 or $100 off NEW Pro 2 Plus+.
  • I’m also hosting a Beautycounter Pop-Up with my friend the Rogue Pharmacist. They have a great day 15% off site wide. I love the new CounterTime Collection & the Overnight Resurfacing peel , Shop through Monday December 2nd.

Chocolate Zucchini Muffins

Summer will be officially here this week. It seems like Ohio forgets how summer is supposed to be. 🙂 Last year on Father’s Day it was 95+ degrees and this year we walked into church and it was 68. Not totally complaining, but the forecast this week does look a bit gloomy and we are ready for the pool at Grandma and Grandpa’s next weekend! This week my friend Katie Mathews is sharing a delicious muffin recipe here on the blog. Katie and I met at a local photography class this summer. She is so sweet and you must follow her on Instagram @FarelyRooted, her food is amazing, beautiful, and healthy! Enjoy Katie’s post below and have a blessed Father’s day to all the Dad’s out there!

Dr. Hartzler

Summer, we love ya. You’re the most blessed season for wholesome foodies. The farmer’s markets are up and running and bursting with the most beautiful produce we see all year in the Midwest. Bravo, farmers of our communities. You fill our market bags with farm fresh berries, vibrant leafy greens, homemade baked goods, and zucchini the size of our faces. Your work is something to celebrate.

In all my farmer’s market excitement, I always seem to buy so much more face-sized zucchini than a small family can consume in a few days time, so after feasting on said gigantic zucchini for three days, in the form of raw, roasted, zoodles, and more, I still have zucchini to spare and have no desire to put it to waste. Coincidentally, my love for chocolate has not changed at all despite the change of the seasons. 

Enter these delightful GLUTEN AND GRAIN FREE CHOCOLATE TAHINI ZUCCHINI MUFFINS, packed with chocolate and veggies because didn’t you know that they always belonged together? 

Enjoy! ~Katie

Print Recipe
Chocolate Zucchini Muffins
They are soft and sweet and nutrient dense and you’ll feel great about eating them any time of the day. Enjoy them warm with a glass of cold almond milk or a spoonful of peanut butter (my personal favorite), and the satisfaction of knowing that your overspending, for once, has turned out for the best, because chocolate muffins are life, am I right?
Prep Time 15 minutes
Cook Time 25 minutes
Servings
Ingredients
WET INGREDIENTS
DRY INGREDIENTS
OTHER INGREDIENTS
Prep Time 15 minutes
Cook Time 25 minutes
Servings
Ingredients
WET INGREDIENTS
DRY INGREDIENTS
OTHER INGREDIENTS
Instructions
  1. Preheat oven to 350 and grease muffin tin.
  2. Combine wet ingredients in a medium bowl.
  3. Combine dry ingredients in a small bowl.
  4. Add dry to wet ingredients and mix until combined.
  5. Fold in zucchini and 2/3 cup chocolate chips.
  6. Fill muffin tin cups with batter about 3/4 of the way up and top with remaining chocolate chips.
  7. Bake for 20-25 minutes until set (mine were done in 22).
  8. Enjoy immediately while the chocolate is gooey or re-heat in the oven for 5 minutes.
Recipe Notes

Life hack: instead of using all your muscles grating zucchini on your own, chop it and pop it in a food processor for 10 seconds and it will magically grate on its own. After shredding, (very important squeeze out most of the water in a bunch of paper towels so the muffs aren’t too wet).

For those Low-Carb and Keto folks out there:

Share this Recipe

Vacation Meal Planning

We spent the last week in Hilton Head Island, SC, and it was so fun! It was as relaxing as it could be with our 5 y/o and 2 y/o in tow. They were the best little travelers! I was a little nervous about the 10.5 hour drive, which turned into 13, but they were great. We had my husband’s parents join us which is always fun and a huge help! They enjoyed themselves and we got to take some walks together while the kids were sleeping. 


Traveling is pretty much a must in this house, and we try our best to fit it in the budget. We do use a Marriott travel rewards credit card for monthly expenses, but I haven’t quite mastered the travel hacking like the Points Guy.

I grew up going to the beach every year, and when we were little, we often tagged along on my dad’s work trips, especially in the summers. My mom would drive behind him in his service truck. He would work and we would explore. I have only 1 state left to go to, guess which one that this.. Alaska! Between all of the normal travel and a couple driving trips out west we hit all the rest. And my Dad saved all his Holiday Inn points from traveling all the time and converted them to Delta miles and the five of us flew to Hawaii the day after I graduated from high school. 

This post is a little bit more in the life category of this blog, but I wanted to document what we took with us this year for meals so it’s easy to pull up next year. I figured if I was writing it down, I might as well share, since it might help some of you! Generally our plan is to cook at dinner at least 3 times, sometimes 4 times during our week long vacations. When traveling as a family we book places that have full kitchens. This was our first time as a family in Hilton Head, and we stayed at Waterside by Spinnaker. It was a perfect location and had nice pools as well. Cooking several meals saves money and keeps us on track with healthy eating. It’s also nice because we can stay in the pool longer in the afternoon and not have to get “ready for dinner.”

The trick is to make it simple. Most condos or VRBO type places have basic kitchen supplies but you won’t find a Blendtec, immersion blender, muffin pans, etc.  Today I made 4 meals for this week and 3 of the 4 required the Blendtec, so those aren’t on the vacation list.  🙂 

The best part about this trip (ok not the best part) but a convenient part was there was a Kroger on the island, new since the last time we were there. So that meant it was super easy to do Click-list and no roaming around the store after a long day of travel trying to find items. It was also right next to a Whole Foods so we were able to grab a few items Kroger doesn’t carry.

 Here was the menu

Breakfast Ideas: We brought a bag of Pamela’s whole grain gluten free mix, so we made pancakes a few mornings and I also made chocolate chip cookie bars with it as a treat later in the week. Funny the ingredients weren’t much different between the pancakes and bars, just different ratios + dark chocolate chips. 🙂 I sort of follow the pancake recipe on the back but add almond butter and applesauce and they are perfect!

Our son loves Applegate Farms chicken and apple sausages so we got those, The weekend before the trip, I had frozen these morning glory muffins, so we had a dozen of those that we brought with us for other days. We purchased some frozen fruit and avocado so we had some collagen fruit smoothies too. The ingredients doubled for popsicles too! Eggs and bacon are super easy as well. We did eat breakfast out once at The French Bakery Hilton Head and it was amazing! See my instagram feed for pictures. 

Lunch Ideas: Chicken Salad, Applegate Farms- Grass fed beef hot dogs, guacamole (pre-made from the store), salad (I brought a few Primal Kitchen Dressings from Thrive Market), some Boar’s Head lunch meat, fruit, raw veggies, or leftover dinner. 

Easy Dinners:

  1. Bunless Burgers – Hawaiian style with Grilled Pineapple on top, with Roasted Cabbage (use olive oil instead of Canola oil)  
  2. Spaghetti Squash and Meat-sauce- Muir Glen Organic Pasta sauce, Meat of your choice (or Veggie Version), + Roasted Spaghetti Squash. Condos don’t have the greatest knives, so microwaving the squash a few min before cutting can be helpful! We also had a bag of frozen broccoli, carrots, and cauliflower steamed to go with it. 
  3. Grilled Chicken, Baked Sweet Potatoes, steamed veggies from above. 

On Mother’s Day we enjoyed dinner out at Chow Daddy’s Hilton Head, the roasted veggie hot bowl with grilled fish was very good. Another night we checked out Giuseppis Pizza, I had the gluten free cauliflower crust pizza (Kale Pesto version!), and the last night we had a local Mexican restaurant called Amigos Cafe Y Cantina. It was literally right across the street and a friend had texted me that week to recommend it. It was a small, authentic mexican restaurant. It was fun to practice our Spanish too. 

A couple other tips: I brought 3-4 seasonings (mostly Trader Joes Blends), a small 8 oz mason jar of olive oil and one of apple cider vinegar, some collagen peptides in a baggie (for smoothies and popsicles), popsicle molds, salt and pepper. I also mixed up the seasoning in a small baggie for the chicken salad in advance as well as the seasoning for my burgers, so I just had to dump it in on vacation! My mother-in law also brought raisons, nuts, and seeds for throwing on salads at lunch, in addition to some snacks. She finds the best deals at what we call the “junk stores” in their area. Recently they snagged a whole box of Rx Bars for $2!

If you are traveling with kiddos and need some easy meal ideas for while you are gone, I hope this is helpful. If you happen to be traveling to Hilton Head, check out some of these yummy restaurants too!

Dr. Hartzler

Probiotic FAQ: Part 2

It’s finally Spring in Ohio! Trees are blooming, and it’s warm enough for walking and playing outside. Our daughter learned to ride a bike without training wheels this week and she’s been non-stop asking to go outside. Balance bikes are amazing, she literally tried the real bike for 1 day before she got it after using the balance bike the last few years.

This is the final post in my Probiotic Series at least for now! If you haven’t checked out the other post, please do, it starts with Probiotics 101, then Probiotic FAQ: Part 1 . And now on to Part 2! I also have a post over on my friend Lindsey Elmore’s site you should read as well. Thanks again to my interns Vineeta Rao and Ruth Gunti who worked on this series with me.

I hope these post help explain some of the basics about probiotics and the answer your questions, if you have further questions. Don’t hesitate to reach out.

Dr. Hartzler

If I have histamine intolerance, should I avoid certain strains? If so which ones?

Histamine intolerance is a condition in which the body has imbalanced levels of histamine. In this state, through the body’s own metabolic processes or consumption of histamine-rich foods, the body has too much histamine and may react to certain food with allergic-like symptoms such as hives, skin rashes, and other digestive symptoms.1 Gut bacteria are involved in both producing and degrading histamine, and having too many histamine-producing bacteria or too little histamine-degrading bacteria may cause elevated histamine levels.2,3 Therefore, it is crucial to select a probiotic that contributes to the proper balance of histamine in the body.

If you have histamine intolerance, it is important to avoid certain species of histamine-producing bacteria when selecting a probiotic. Those that should be avoided are Lactobacillus casei, Lactobacillus Bulgaricus, Streptococcus thermophilus, Lactobacillus delbrueckii, Lactobacillus helveticus.3
In contrast, certain probiotics appear to aid in relieving the imbalances found with histamine intolerance. Lactobacillus rhamnosus strains GG and c705 have been observed to inhibit the effect of histamine in the body.4 Additionally, in vitro studies suggest that bifidobacterium lactis and lactobacillus plantarum species promote histamine breakdown. 5,6

Should I take a probiotic while also taking an antibiotic? If so which one, and for how long?

Although clinicians have generally supported using probiotics with an antibiotic course, this is an area of controversy as new studies suggest that probiotics may interrupt the body’s natural process of restoring the bacterial balance in the gut. There are many studies that support using probiotics to prevent antibiotic-associated diarrhea, and among the tested species S. boulardii has specifically been shown to be effective.7 Studies have also shown that Lactobacillus rhamnosus GG, the strain contained in the Culturelle probiotic, appears and effective to prevent antibiotic associated diarrhea (AAD) in an outpatient setting.8 The recommended  dose is 107 to 1010 colony-forming units (CFU) per capsule (taken one to 3 times daily) as that is what has been studied; duration of therapy can be 1-3 weeks or the entire length of time that the patient is on antibiotics.9 For reference, Metagenics “UltraFlora LGG” and Culturelle “Digestive Health” products contains 1010 CFU per dose, and Culturelle “Kids” product contains 109 CFU per dose, making these products good choices for AAD.10 It is generally recommended to take probiotics for a couple months after therapy and consuming fermented foods. Overall it is said that “probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics.” 8-10

However, there is emerging research that suggests that probiotics may actually delay spontaneous recovery of the microorganisms in the gut, or the “gut microbiome.” A recent study compared spontaneous gut recovery to probiotic use in humans receiving a broad-spectrum antibiotic course. By performing endoscopies and examining the stool from the patients before and after receiving antibiotics, normal genetic expression of bacteria in the gut was delayed by up to 5 months in the probiotic group versus a matter of weeks in the group allowed to spontaneously recover.11,12 The in vitro portion of the study suggested that Lactobacillus acidophilus may inhibit the native gut microbiome.11 While this study cautions against the preventative use of probiotics with an antibiotic course, further studies to shed light on the benefit or harm of probiotics are needed to come to a clear conclusion.12

In the meantime, it may be wise to avoid probiotics with Lactobacillus acidophilus when taking an antibiotic course. One of the challenges as a provider recommending probiotics is that this was just 1-2 studies in the midst of all the literature and didn’t not look at saccharomyces boulardii and its effect, therefore it really just raises questions for future research and gives us a pause to our practice of using blanket probiotics for everyone on antibiotics habit.

If I have dysbiosis or Small intestinal bacterial Overgrowth, should I avoid pre-biotics or certain probiotic strains?

Small Intestinal Bacterial Overgrowth (SIBO) typically refers to a form of dysbiosis (imbalance of bacteria on the body) attributed to an excessive overgrowth or changes in types of bacteria in the small-intestine.13,,14 While the small intestine is not sterile, it has far fewer bacteria than the large intestine. Thus, SIBO may result from the specific bacteria that normally grows in the large intestine growing inappropriately in the small intestine.13,14 Other causes of SIBO include multiple courses of antibiotics and impaired defense mechanisms such as low stomach acid, which may be caused by use of Proton Pump Inhibitors (PPIs). While the definition is constantly changing and expanding to include other forms of dysbiosis, SIBO is typically characterized by non-specific gastrointestinal symptoms such as bloating, abdominal discomfort, diarrhea, fatigue, and weakness and might be treated with an antibiotic course.13,14

There are several studies that actually support the use of probiotics for this disorder.15  However, at the moment there is little consensus across the studies as to which probiotics species and strains will provide benefit for SIBO. Regardless of the species, the theoretical concern with using probiotics in SIBO even if the bacteria added to the gut is “good” bacteria, too much bacteria often produces symptoms of bloating and gas, which would worsen symptoms. In SIBO, patients often have an overgrowth of D-lactate-producing bacteria, so it may be best to avoid probiotics that also produce D-lactate such as Lactobacillus acidophilus.16

In the past it has also been generally recommended that one avoid the use of prebiotics until SIBO symptoms under control. Currently, studies that challenge this notion are frequently emerging, and in time, we may see a demonstrable benefit of certain probiotics and prebiotics in SIBO.16 However, until studies show which species and strains relieve rather than aggravate SIBO symptoms, it is likely best to avoid prebiotics and probiotics that produce D-lactate. In general, I recommend treating the overgrowth before working on replacing the flora with probiotics. Once those probiotics are tolerated, consider adding prebiotics to support healthy growth of gut flora along with other measures to prevent SIBO recurrence. Specifically, Partially Hydrolyzed Guar Gum (PHGG) is a prebiotic that has been shown to treat SIBO when administered alongside the antibiotic rifaximin better than rifaximin alone.17 Thus, this product could be a good option for encouraging healthy gut flora growth.

That’s a wrap. As always you can find great probiotic options on my FullScript Store or at YoungLiving. Feel free to message me if you have specific questions. We have so much science but we are still not quite a place were we absolutely know which probiotic product is going to work for each person. We are moving closer to that each day.

References:

  1. Maintz L,  Novak N.Histamine and histamine intolerance.Am J Clin Nutr. 2007;85(5):1185-96.
  2. Pugin B, Barcik W, Westermann P, et al. A wide diversity of bacteria from the human gut produces and degrades biogenic amines. Microb Ecol Health Dis. 2017;28(1):1353881.
  3. What causes Histamine Intolerance. Facts vs Fitness. https://factvsfitness.com/probiotics-histamine-intolerance/. Updated July 27, 2017. Accessed January 23, 2019.
  4. Oksaharju A, Kankainen M, Kekkonen RA, et al. Probiotic Lactobacillus rhamnosus downregulates FCER1 and HRH4 expression in human mast cells. World J Gastroenterol. 2011;17(6):750-9.
  5. Mokhtar S., Mostafa G, Taha R. et al. Effect of different starter cultures on the biogenic amines production as a critical control point in fresh fermented sausages. Eur Food Res Technol. 2012;235(3): 527-535.
  6. Capozzi V, Russo P, Ladero V, et al. Biogenic Amines Degradation by Lactobacillus plantarum: Toward a Potential Application in Wine. Front Microbiol. 2012; 3: 122.
  7. Mcfarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010;16(18):2202-22.
  8. Blaabjerg S, Artzi DM, Aabenhus R. Probiotics for the Prevention of
    Antibiotic-Associated Diarrhea in Outpatients-A Systematic Review and Meta-Analysis. Antibiotics (Basel). 2017 Oct 12;6(4).
  9. Rodgers B, Kirley K, Mounsey A. PURLs: prescribing an antibiotic? Pair it with probiotics. J Fam Pract. 2013;62(3):148-50.
  10. Antibiotic Use & Associated Diarrhoea Prevention. Probiotic Advisor. https://www.probioticadvisor.com/ Accessed February 9, 2019.
  11. Suez J, Zmora N, Zilberman-Schapira G, et al. Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT. Cell. 2018;174(6):1406-1423.
  12. Kresser C. RHR: What the Latest Research Says about Probiotics, with Lucy Mailing. https://chriskresser.com/what-the-latest-research-says-about-probiotics-with-lucy-mailing/ Updated November 4, 2018. Accessed February 9, 2019.
  13. Drake LE, Guilliams TG. Small intestinal bacterial overgrowth (SIBO): diagnostic challenges and functional solutions. Point Institute. 2018;14(2)1-15.
  14. Kresser C. What Causes SIBO (Small Intestinal Bacterial Overgrowth) and Why It’s So Hard To Treat. https://chriskresser.com/sibo-what-causes-it-and-why-its-so-hard-to-treat/ Updated November 4, 2014. Accessed February 9, 2019.
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