​Whether its an experiment or doctor’s orders, going gluten-free is an adjustment. Removing gluten may mean eliminating not only some of your favorite foods, but possibly a good portion of your current diet. What foods will you eat in their place? How will you fill the gluten void?

Most likely, there’s no lack of “gluten-free” versions of your favorite foods on your grocer’s shelves. In fact, the number of gluten-free packaged foods is exploding to keep up with consumer demand. Going gluten-free may be as easy as buying and opening a different box—or bag or carton.

But are gluten-free packaged foods the answer? Possibly not. In fact, they may be the surprising reason behind many go-gluten-free resolutions. Here’s why.
​

• Cost: Gluten-free packaged goods cost more than their conventional counterparts, sometimes up to 30% more. The added cost of a gluten-free version may be worth it when trying to marry compliance and your favorite meal or for a special occasion. But buying gluten-free products by default could strain your wallet. Compare prices and buyer beware!
• Calories: Gluten proteins provide the satisfying texture of so many foods, making baked goods bounce and giving pasta its chewiness. Therefore, when a gluten-containing food is manufactured as a gluten-free version, something needs to be added to create a palatable and flavorful product. Most often gluten-free versions will have added saturated fat, sugar, and sodium. So it is not uncommon to gain weight on a gluten-free diet, which relies on gluten-free packaged foods. “Gluten-free” doesn’t mean a product is low-calorie. So be sure to read the nutrition facts, or gluten-free products may strain your belt and blood pressure as well.
• More (not less) processed: Most people go gluten-free for health reasons. But many gluten-free processed foods are actually more processed and less nutrient-dense than their gluten-containing counterparts. Without gluten for elasticity and chewiness, these products often rely on gums, starches, and stabilizers. Always read labels.
• Your gut might not like it: It is not uncommon for individuals to experience gastrointestinal distress from gluten-free foods. The gums, starches, stabilizers, and many gluten-free alternate flours can cause bloating and other digestive issues. If your gut isn’t happy, reevaluate.
• Is it really gluten-free? The Food and Drug Administration requires that products labeled “gluten-free” contain less than 20 parts per million of gluten. However, be cautious of labels stating “low gluten,” “no gluten,” and “naturally gluten-free,” as these terms are not regulated.

There’s a better way. Don’t just swap out one package for another. Relying on gluten-free packaged foods can be taxing on your budget, blood pressure, waistline, and digestion. Rather, consider this an ideal time to shift your diet away from processed foods and toward more whole foods. Instead, give your diet a bona fide upgrade. 

​Reference:
Financial Times, Going gluten free: one of 3 trends shaking up commodities https://www.ft.com/content/5348432e-1a13-11e7-bcac-6d03d067f81f, Accessed December 9, 2017.

Urological health is vital to every man’s well being. Learn what urologists do and when to see one.When was the last time you scheduled an appointment with a urologist?

Urology is the branch of medicine that focuses on the health of the urinary-tract system, in addition to male reproductive health. While consulting a doctor who specializes in these areas may make you uneasy or uncomfortable, it shouldn’t.

You see, urological health is vital to your well being. And your urologist is meant to be a healthcare partner who looks out for your best interests in those areas of your body.

What do urologists examine?
Urologists are trained to examine, manage, and treat the urinary tract and male reproductive system. As the name indicates, the urinary system, (also known as the renal system or urinary tract) eliminates urine, controls electrolytes, and regulates blood pressure and blood pH. It consists of the following organs:1

• Adrenal glands: glands that release hormones, located on top of the kidneys

• Bladder: the muscular, hollow sac in the pelvis that stores urine

• Kidneys: organs that filter and remove waste from the blood and subsequently produce urine

• Ureters: tubes that transport urine from the kidneys to the bladder

• Urethra: a tube where urine exits the body from the bladder

Urologists treat symptoms involving these organs as well as those involving the male reproductive system: the penis, prostate, and  testicles. The areas they often focus on include:2

• Enlarged prostate: An enlarged prostate isn’t completely out of the ordinary as men get older, but that doesn’t mean it’s comfortable. An enlarged prostate can lead to blocked urine flow, increased frequency of urination (especially at night), difficulty starting urination or a weak flow, or inability to completely empty the bladder. To address these issues, a urologist might examine the prostate and offer prescriptions to relieve symptoms. Minimally invasive procedures or surgery can be performed if needed.3

• Prostate cancer screening: Men should talk to a urologist about the benefits of routine prostate screenings. Just having one prostate-specific antigen (PSA) test in your 40s can help predict your overall risk of prostate cancer, as well as determine the course of action your urologist might take moving forward. If your PSA is 0.7 or lower, your risk of prostate cancer is at less than 10%, and you may only need to be screened every five years.2 Conversely, men with a PSA of 1 or higher require more frequent screening.2

• Erectile dysfunction: While the cause of erectile dysfunction isn’t always physical, a urologist can perform a blood test, check your hormones, and usually prescribe a solution that will increase blood flow to the penis. Since the condition could be a sign of  other health problems, your urologist may take this opportunity to also assess any potential risks for hypertension, renal failure, and/or vascular conditions.4

• Vasectomy: This safe, voluntary outpatient procedure is ideal for men who no longer wish to conceive children. Before scheduling a vasectomy, men should consult with their urologist for more information and understand the pros and cons. The practitioner can offer insights into the procedure and  help the patient make an informed decision.

These are just a few of the more common reasons patients may be seen by urologists.  

Why see a urologist?
Urologists may be able to recommend preventative measures to encourage good urological health, uncover (or resolve) male reproductive issues, and treat urinary infections or illnesses.4 Whether you’re facing a minor issue or a chronic health problem, you’ll want to know exactly what’s going on in that area of your body—and a urologist can help keep you healthy.

While some people might associate urology with pain, this is more of a stereotype than a reality. During most invasive procedures, men can expect an anesthetic to numb the affected area. Admittedly, patients might feel pressure or movement from time to time, but they shouldn’t experience pain or significant discomfort.

Early detection for any illness is crucial, so don’t let your worries take over common sense. Men in their 40s and 50s—if they aren’t already doing so—should start seeing their urologist regularly to stay on top of their urological health.

This content is not intended as a substitute for professional medical advice, diagnosis, or treatment. Individuals should always consult with their healthcare professional for advice on medical issues.
​
References:

1. Healthline Staff (n.d.). Faces of Healthcare: What Is a Urologist? Healthline. Accessed December 21, 2018.
2. Klein E. Men Over 40: Start Seeing a Urologist Regularly. Cleveland Clinic. 2013. Accessed December 21, 2018.
3. National Association for Continence. https://www.nafc.org/enlarged-prostate/. Accessed January 17, 2019.
4. Park H. The World Journal of Men’s Health. 2017;35(2):57-58.

​
​Submitted by the Metagenics Marketing Team

By Bronwyn Storoschuk, ND

As human life expectancy continues to increase, there is also an increased risk for cognitive impairment over the course of a longer life.1 Brain health and cognitive performance have received a lot of recent attention by researchers in order to understand, and develop, strategies that will reduce the risk for cognitive decline.2 Furthermore, greater importance is being placed on “healthspan” versus “lifespan,” and there is an increased demand to find ways to optimize overall health, including brain health and cognitive performance.

In the past few years, more scientific interest on the influence of nutrition on brain health and function has emerged, especially as dietary fats have regained popularity among consumers.2 It has been well-documented that a ketogenic diet can have profound benefits on the brain and cognitive function; however, there is also evidence that suggests consuming a high-fat diet increases the risk of cognitive decline and may impair brain performance.2,3 To clear some of the confusion, it is important to differentiate between the different types of fats and the potential mechanisms that may explain impairment in cognitive function.  
As far back as 1990, animal studies showed that diets high in saturated fats caused significant impairments in learning and memory.4 The results from subsequent human studies showed similar findings. Research showed that high-fat diets, containing mostly omega-6 fatty acids and saturated fats, were associated with worse performance on cognitive tasks.5 In addition, diets that contained mostly saturated fats and transfats have been associated with an increased risk of brain disorders.6 It has also been determined that high-fat diets with elevated amounts of saturated fats and cholesterol may impair intellectual function, along with increased risk for other health concerns.7 As most Americans follow a “Standard American Diet,” which contains high amounts of omega-6 fatty acids, saturated fats, and transfats and low omega-3 fatty acids, it is not surprising that rates of cognitive decline are increasing in the US.2,8

In the United States, the major sources of saturated fats come from:9

• Fatty cuts of meat
• Pastries and baked goods
• Cheese
• Milk
• Margarine
• Salad dressings
• Mayonnaise
• Butter

The major sources of trans fats, which are primarily industrially produced from vegetable oils, are found in:10

• Baked goods like cakes and cookies
• Crackers
• Margarine
• Fried foods
• Potato chips
• Popcorn  
• Shortening

Omega-6 fatty acids are found in many commonly used plant oils including canola, safflower, sunflower, soybean, corn, and cotton seed oil.11 In the Standard American Diet the consumption of vegetable oils is significant; thus omega-6 fatty acid consumption has become much higher than omega-3 fatty acid intake.11 The suggested dietary intake of omega-6:omega-3 ratio is around 1-4:1; however, most Americans consume these fats within the range of a 10:1 to 20:1 ratio.11 Although omega-6 fatty acids are essential, meaning the human body requires them for good health but cannot synthesize them, and they must be eaten to provide benefits, once consumed, they are metabolized into arachidonic acid, which at excessive levels is proinflammatory.11 In recent years, research has attempted to determine the biological mechanisms behind the detrimental cognitive effects associated with a high-fat diet. The major proposed mechanisms include insulin resistance, oxidative stress, and inflammation.2

Insulin resistance
Although insulin is usually discussed in relation to carbohydrate intake, consumption of both saturated and trans fats have been studied to impair insulin sensitivity.12 In addition, data have shown diets high in saturated fats are associated with increased total body weight and abdominal obesity, which also contribute to insulin resistance.13 Overall, it has been found that cognitive performance declines as whole body insulin resistance increases.10

It is important to consider that the Standard American Diet is also comprised of large amounts of refined sugars and refined grains.2 Increased consumption of refined carbohydrates also leads to insulin resistance, the greatest effects of which are seen when high sugar intake is combined with excessive caloric intake—often found in conjunction with a high-fat diet.14 So although specific fats can induce insulin resistance, this combination is more detrimental and very common in the US population.2

Oxidative stress
It has been observed that a high-fat diet, primarily composed of increased intakes of saturated fats and omega-6 fats, raises the levels of free radicals in tissues and the brain.11,15 Free radicals, or reactive oxygen species (ROS), contribute to oxidative stress and lead to cellular damage.16 Chronically high levels of oxidative stress are known to lead to cognitive decline.16 Research has shown that high-fat diet-induced oxidative stress also leads to reduced levels of brain-derived neurotrophic factor (BDNF), which plays an important role in the survival, and growth, of brain cells and may explain some of the impairment in cognitive performance.2,17 Interestingly, data from preclinical studies indicate vitamin E, a potent antioxidant, is associated with better cognitive performance.18,19 While these findings still need to be confirmed in human studies, this information suggests that oxidative stress is involved in cognitive impairment and may be an outcome of a high-fat diet.2

Moreover, high-fat diets, specifically the fats included in the Standard American Diet, commonly lack essential vitamins, minerals, and antioxidants, which may further limit the body’s ability to effectively combat the increased levels of oxidative stress resulting from this high-fat diet.20

Inflammation
Studies show high-fat diets composed primarily of saturated fats and omega-6 fatty acids have been associated with significantly increased levels of inflammation both systemically and in the brain.2 The brain is very sensitive to levels of inflammation, as inflammatory mediators can easily cross the blood-brain barrier.2 In one animal study, a diet comprised of 60% saturated fat showed significantly increased levels of inflammatory mediators, reduced levels of brain-derived neurotrophic factors, and highly reactive cells in the brain. As inflammatory mediators increased, significant impairment in cognitive performance was observed.21

Fats & cognition
​It is clear that all fats are not created equally. For instance, a diet that is rich in omega-3 fatty acids has been found to support cognitive processes.11 Accordingly, diets high in omega-3 fatty acids are associated with enhanced memory and learning and may play a role in supporting healthy cognition.24-25 The most important omega-3 fatty acids for brain health are EPA and DHA.26 However, it can be challenging to get the appropriate intake of EPA and DHA by diet alone, especially when looking to enhance cognitive performance.26 Also, it is important to note that a low intake of total fat, less than 20% of caloric intake, has been studied to impair cognitive performance due to an inadequate intake of fat-soluble vitamins and essential fatty acids, all of which are necessary to support cognition and general health.10

Regardless of what diet is followed, when fat is consumed, it is very important to choose the right fats. Brain function is impacted by insulin resistance and is sensitive to oxidative stress and inflammation, all of which are increased on a high-fat diet.2 However, this does not mean that all types of fats are bad, as it is well-documented that omega-3 fatty acids support  cognition, and fat, in general, is required for optimal brain health.24

This content is not intended as a substitute for professional medical advice, diagnosis, or treatment. Individuals should always consult with their healthcare professional for advice on medical issues.

References:

1. Suthers K et al. Gerontol B Psychol Sci Soc Sci. 2003;58(3):S179-186.
2. Freeman L et al. Nutr Neurosci. 2014;17(6):241–251.
3. Hernandez A et al. Front Aging Neurosci. 2018;10:391.
4. Greenwood CE et al. Behav Neural Biol. 1990;53:74–87.
5. Kalmijn S et al. Ann Neurol. 1997;42:776–782.
6. Luchsinger JA et al. Arch Neurol. 2002;59:1258–1263.
7. Requejo AM et al. Eur J Clin Nutr. 2003;57(Suppl 1):S54–57.
8. Simopoulos AP. Biomed Pharmacother. 2002;56:365–379.
9. Subar AF et al. J Am Diet Assoc. 1998;98:537–547.
10. Dhaka V et al. J Food Sci Technol. 2011;48(5):534–541.
11. Patterson E et al. J Nutr Metab. 2012;2012:539426.
12. Ghafoorunissa G. Asia Pac J Clin Nutr. 2008;17:212–215.
13. Frankenberg A et al. Eur J Nutr. 2017;56(1):431–443.
14. Macdonald I. Eur J Nutr. 2016;55(Suppl 2):17–23.
15. Beltowski J et al. J Physiol Pharmacol. 2000;51:883–896.
16. Zhu X et al. Cell Mol Life Sci. 2007;64:2202.
17. Bathina S et al. Arch Med Sci. 2015;11(6):1164–1178.
18. Lockrow J et al. Exp Neurol. 2009;216:278–289.
19. Wu A et al. Eur J Neurosci. 2004;19:1699–1707.
20. Greenwood CE et al. Neurobiol Aging. 2005;26(Suppl 1):42–45.
21. Pistell P et al. J Neuroimmunol. 2010;219(1-2):25–32.
22. Simopoulos AP. J Am Coll Nutr. 2002;21(6):495-505.
23. Uranga RM et al. J Neurochem. 2010;114:344–361.
24. Schaefer EJ et al. Archives of Neurology. 2006;63(11):1545–1550.
25. Freeman MP et al. Journal of Clinical Psychiatry. 2006;67(12):1954–1967.
26. Swanson D et al. Adv Nutr. 2012;3(1):1–7.

Bronwyn Storoschuk, ND 
Bronwyn Storoschuk, ND is a board-certified naturopathic doctor trained at the Canadian College of Naturopathic Medicine. Prior to attaining her ND, Dr. Storoschuk completed her Bachelor of Science (Honours) in Kinesiology at Queen’s University in Kingston, Ontario. She currently works in private practice in Toronto, Ontario. One of her practices is located within an integrative fertility clinic, where she provides naturopathic care to individuals undergoing assisted reproductive technology (ART). Dr. Storoschuk integrates evidence-based medicine with the understanding of the body’s natural physiology and innate healing wisdom. She is passionate about empowering women to take control of their hormonal health and has a clinical focus in hormone balance, reproductive health, and fertility.

​Dr. Storoschuk is a paid consultant and guest writer for Metagenics.

​Your body is built to fight off anything that may harm it, from infections to injuries to toxins in the air. And when your body is in danger, your immune system to triggered to respond.1 That response is called inflammation—i.e., your body’s way of protecting and healing itself.2 Eventually, you become healthy again. But what if you don’t?
For some, inflammation can become chronic and persist; instead of becoming your ally, it becomes your worst nightmare.3 In fact, systemic inflammation is a known precursor to chronic illness.4,5
Unfortunately, chronic inflammation may be more common than you think. An otherwise healthy person can have a low to moderate amount of inflammation in his or her body and not even know it. The good news? There are plenty of foods you can eat that have been shown to help reduce chronic inflammation and can therefore promote overall health; there are also plenty of foods that have been linked to promoting inflammation which you can avoid. Keep these lists in mind at your next meal!

Do eat:

Leafy greensVegetables such as broccoli, spinach, and kale are packed with antioxidants that protect your body from foreign invaders.4,6

BerriesVarieties including blueberries, raspberries, cherries, and strawberries are high in protective compounds such as antioxidants and polyphenols.4,7

NutsHealthy snacks like almonds and walnuts have been associated with reduced markers of inflammation.4

AvocadoA superfood rich in monounsaturated fats as well as carotenoids and tocopherols, avocados can reduce your risk for chronic illness.9,10

Dark chocolateA delicious treat with plenty of antioxidants to fight off inflammation. It may even lead to healthier aging.1

Green teaSip on this ultrahealthy drink for its antioxidative, anti-inflammatory properties, particularly its high levels of epigallocatechin-3-gallate (EGCG). This substance inhibits proinflammatory cytokine production.12,13

Fatty fishOmega-3 fatty acids found in fatty fish (e.g., salmon) are metabolized into anti-inflammatory compounds called resolvins.4,14

Extra virgin olive oilThis kitchen staple is full of healthy monounsaturated fats and has been shown to reduce inflammatory markers.4

TurmericThis beloved spice contains curcumin, a powerful anti-inflammatory nutrient.8

CoffeeYour favorite morning beverage contains polyphenols and other anti-inflammatory compounds.

Note: Many of the foods on this list make the cut in one of the most well-researched diets in the world—the Mediterranean diet. Overall, the plant-based combination of healthy fats, carbs, and protein is shown to reduce key markers of inflammation.4,15-18

Eat less:
Saturated fatsFound in virtually all processed, packaged junk foods as well as things like shortening and lard, saturated fats can throw off immune cells and trigger inflammation. Common culprits include pizza, pasta, cheese, and red meat products.19

Refined carbsThese include white flour (breads, rolls, and crackers), white potatoes (French fries), and many breakfast cereals, which contain a high glycemic index.4,21

Processed meatsConsumption of processed red meats (burgers, hot dogs, and sausage) has been associated with increased levels of inflammatory markers.4,22

SugarForego anything that rhymes with gross (e.g. fructose, sucrose), as these can trigger the release of cytokines and lead to inflammation. 4,18

Omega-6 Fatty Acids
Found in corn, safflower, sunflower, peanuts, soy, vegetable oils, mayonaise and many commercial salad dressings, these fatty acids may inhibit the anti-inflammatory effects of healthy omega-3s. 20


With this information in mind, incorporating more of these plant-based foods and healthy fats into your diet while cutting out sugar and processed foods can be a powerful strategy in supporting your long-term health.
This information is for educational purposes only. This content is not intended as a substitute for professional medical advice, diagnosis, or treatment. Individuals should always consult with their healthcare professional for advice on medical issues.
References:

1. Stoecklein VM et al. J Leukoc Biol. 2012;92(3):539-551.
2. Nordqvist C. Medical News Today. https://www.medicalnewstoday.com/articles/248423.php. Accessed March 11, 2019.
3. Han S. Healthline. https://www.healthline.com/health/chronic-inflammation. Accessed March 7, 2019.
4. Harvard Medical School. Harvard Health Publishing. https://www.health.harvard.edu/staying-healthy/foods-that-fight-inflammation. Accessed March 8, 2019.
5. Minihane AM et al. Br J Nutr. 2015;114(7):999–1012.
6. Guerrero-Beltrán CE et al. Exp Toxicol Pathol. 2012;64(5):503-508.
7. Joseph SV et al. J Agric Food Chem. 2014;62(18):3886-3903.
8. Chainani-Wu N et al. J Altern Complement Med. 2003;9(1):161-168.
9. Lu QY et al. J Agric Food Chem. 2009;57(21):10408-10413.
10. Donnarumma G et al. Inflammation. 2011;34(6):568-575.
11. Becker K et al. Front Pharmacol. 2013;4:154.
12. Tipoe GL et al. Cardiovasc Hematol Disord Drug Targets. 2007;7(2):135-144.
13. Molina N et al. Int Immunopharmacol. 2015;28(2):985-996.
14. Weylandt KH et al. Prostaglandins Other Lipid Mediat. 2012;97(3-4):73-82.
15. Casas R et al. PLoS One. 2014;9(6):e100084.
16. Casas R et al. Endocr Metab Immune Disord Drug Targets. 2016;14(4):245–254.
17. Sofi F et al. Am J Clin Nutr. 2010 Nov;92(5):1189-1196.
18. Giugliano D et al. J Am Coll Cardiol. 2006;48(4):677-685.
19. Weiler N. University of California San Francisco. https://www.ucsf.edu/news/2016/03/401906/saturated-fat-short-circuits-immune-cells-trigger-inflammation. Accessed March 8, 2019.
20. Innes JK et al. Prostaglandins Leukot Essent Fatty Acids. 2018;132:41-48.
21. Hu FB. Am J Clin Nutr. 2010;91(6):1541–1542.
22. Weiwan C et al. J Am Coll Nutr. 2017;36(5):378–385.
23. Waldschmidt TJ et al. Alcohol. 2008;42(2):137–142.

Submitted by the Metagenics Marketing Team

​Q&A: What Should I Look for in a Hemp Oil?
It seems like hemp products are everywhere you look. With so many options to choose from, it’s more important than ever to ask the right questions when seeking a hemp product.

Q. What is the composition of the product?
A. The Cannabis sativa plant contains more than 80 different phytocannabinoids, which are  naturally occurring plant-based bioactive compounds that can support and influence the body’s  endocannabinoid system (ECS). The ECS promotes biological balance in many cells and tissues throughout the body.

While certain phytocannabinoid compounds may be more well-known, research has indicated that several of the phytocannabinoids found in hemp may work together to produce synergistic effects on the body’s ECS. Terpenes, a group of compounds naturally present in all plants and spices including pepper, cloves, and cinnamon, are also thought to carry a wide array of health supportive properties. Terpenes work together with phytocannabinoids to enhance the overall benefit of hemp oil and support physiological health.This synergy is known in the research community as the entourage effect. Ultimately, healthcare practitioners can best advise on which compounds people might seek for their personal support needs.

Q. How much information does the manufacturer provide on the product?
A. This is where manufacturing transparency comes in. It’s vitally important to purchase any product from a trusted source. If you can access data from testing conducted on the product, it will provide added peace of mind. 

Q. What extraction methods were applied?
A. Did you know there are multiple ways extracts can be obtained from plants? Conventional methods commonly using alcohol or solvents are generally more cost-effective and rapid from a manufacturing standpoint. Other more costly and time-consuming methods can include supercritical extraction. Supercritical extraction uses pressure to extract the desired compounds from a plant. The most well-known form of supercritical extraction utilizes carbon dioxide and is termed “supercritical CO2 extraction.” Unlike many conventional extraction methods, the supercritical CO2 extraction process is free of any harsh chemical solvents. CO2 extraction is also thought to be a more environmentally friendly method as compared to conventional methods.
​
References available
Submitted by the Metagenics Marketing Team

BY RUTH KIRK-GARCIA | IMMUNE, INFLAMMATION | 0 COMMENT
Inflammation is the body’s initial response to cell damage and is designed to protect it from infection or further injury. Like day and night, the inflammatory process is a cycle defined by two halves – initiation and resolution.
The initiation phase begins with a local dispatch of immune cells at the site of damage, which sounds the alarm, igniting inflammation within the surrounding tissue. Once the threat of infection or damage is neutralized, the resolution response is activated, calming the initial phase of inflammation and facilitating cellular repair and recovery.
​
Unresolved Issues
The transition between initiation and resolution is required to complete the cycle of inflammation and to promote healing. However, for some people, this transition fails to occur, leading to a chronic, sustained inflammatory response. This keeps the body in the initiation phase where it cannot resolve inflammation; like a loud alarm system with a broken ‘deactivate’ button. The result? A state of unremitting inflammation that keeps the body in a cycle of tissue damage, preventing recovery.
However, for some people, this transition fails to occur, leading to a chronic, sustained inflammatory response. This keeps the body in the initiation phase where it cannot resolve inflammation; like a loud alarm system with a broken ‘deactivate’ button.

A Remedy for Resolution
If you or someone you know suffers from an inflammatory condition (such as arthritis), you will no doubt be aware of the frustration that comes from persistent symptoms, despite your efforts to find a solution. You may be doing all the right things, taking the right medications, taking steps to improve your diet, exercise and sleep, while proactively managing your stress. However, if the resolution of inflammation is impaired, you will continue to experience symptoms, as the inflammatory response cannot be ‘deactivated’. It’s no wonder that cutting-edge research in the field of inflammation resolution is turning heads, particularly in regards to a group of compounds called specialized pro-resolving mediators (SPMs).

Send in The SPMs
As their name suggests, SPMs trigger or ‘deactivate’ the resolution phase of inflammation in the body,[1] which are produced from omega-3 fatty acids, (EPA) and docosahexaenoic acid (DHA).[2] Like a half-time speech that inspires a triumphant victory, SPMs motivate the immune system to promote resolution. In the initiation phase, white blood cells are known as macrophages actively destroy problem microbes and clear the excess of immune cells released during inflammation. However, in the resolution phase, SPMs reprogram these macrophages, switching their game plan from offence to defense to help regenerate and repair damaged tissue.[3] This results in resolution, relief and recovery.
So why, if the body can produce SPMs, does inflammation remain unresolved? Research tells us that the body’s ability to produce SPMs is lower in conditions involving chronic inflammation,[4] meaning that in highly inflamed individuals, the ability to resolve inflammation is likely to be impaired. Some pharmacological anti-inflammatories (even some used to treat inflammation) may also prevent SPM activity,[5] as they inhibit inflammation preventing the body’s ability to activate the resolution phase.  This is why supplements providing SPMs are an exciting development for chronic inflammation sufferers; as restoring SPM levels goes beyond the effects of conventional treatments to actively promote resolution and full circle recovery.
This is why supplements providing SPMs are an exciting development for chronic inflammation sufferers; as restoring SPM levels goes beyond the effects of conventional treatments to actively promote resolution and full circle recovery
Viva la Resolution!
Heralding a new era of healing, SPMs offer a beacon of hope for those suffering from chronic inflammation, offering a new solution for achieving resolution! For more information on natural management of inflammation, read on by clicking here.However, if you are ready to experience the resolving effects of SPMs, contact a Practitioner near you today.

[1] Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G et al. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med. 2002 Oct 21;196(8):1025-37.
[2] Hirahashi J. Omega-3 polyunsaturated fatty acids for the treatment of IgA nephropathy. J Clin Med. 2017 Jul;6(7):70. doi: 10.3390/jcm6070070.
[3] Spite M, Clària J, Serhan CN. Resolvins, specialized proresolving lipid mediators, and their potential roles in metabolic diseases. Cell Metab. 2014 Jan 7;19(1):21-36. doi: 10.1016/j.cmet.2013.10.006. 
[4] Barden AE, Mas E, Croft KD, Phillips M, Mori TA. Specialized proresolving lipid mediators in humans with the metabolic syndrome after n-3 fatty acids and aspirin. Am J Clin Nutr. 2015 Dec;102(6):1357-64. doi: 10.3945/ajcn.115.116384.
[5] Chiang N, Serhan CN. Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors. Mol Aspects Med. 2017 Dec;58:114-129. doi: 10.1016/j.mam.2017.03.005.

What we know for clinical practice and decision making

by Sara Gottfried, MD, and Kari Hamrick, PhD, RD
Polycystic ovary syndrome (PCOS) is a problem of hormone dysregulation that can lead to irregular menstrual cycles, high androgens, and its downstream sequelae such as acne and hirsutism, infertility, weight gain, and cardiovascular disease. As practitioners and their affected female patients anguish over the root cause and solutions, one part is very clear: up to 85% of women with PCOS are insufficient in vitamin D.1 For our patients with PCOS, correcting low serum vitamin D levels can be a helpful lever in improving hormonal, metabolic, inflammatory, and possibly cardiovascular outcomes.
Vitamin D is known as the “sunshine vitamin” because sunlight can trigger cutaneous synthesis of vitamin D. Previously, I reviewed the role of vitamin D in the body and the prevalence of vitamin D deficiency and insufficiency across populations. Vitamin D is a steroid hormone precursor that has hundreds of roles in the body beyond bone health. Having been interested in vitamin D deficiency and the connection with health issues, especially those impacting women, I wanted to delve into the link between vitamin D and PCOS. I will review the current literature to help inform clinical practice and decision making for this unique patient group.

PCOS and women’s health
PCOS is the most common endocrine disorder among women during reproductive years, with an estimated prevalence of 4-18% from puberty to perimenopause.2,3 Prevalence varies based on ethnicity (i.e., in descending order: Black > Middle Eastern > Caucasian > Chinese).4 Clinical presentation may include insulin resistance, obesity, hirsutism (excess male pattern hair growth), and chronic low-grade inflammation.5,6 PCOS has been linked to serious health concerns, including increased risk of breast and endometrial cancers, infertility, heart disease, stroke, dysglycemia, insulin resistance, gestational diabetes, and preeclampsia.5,6

Women experiencing hormonal imbalance at any age may feel out of control and even disempowered. Women seeking help for PCOS deserve compassionate healthcare providers who are able to diagnose, understand the root causes of their symptoms, and provide evidence-based guidelines for measurable and effective health improvement.

Recently updated international PCOS guidelines have made diagnosis and care for patients more comprehensive, standardized, and evidence-based.7 In the summer of 2018, an international consortium of PCOS healthcare professionals, including 37 societies across 71 countries (spanning six continents), issued a guideline for the assessment and management of PCOS, with 31 evidence-based recommendations that help refine the therapeutic approach and increased the focus on the important role of education and lifestyle modification.7

I understand the desire to employ best practices with the most available research evidence in your clinic. But with patients coming and going all day, it is easy to become overwhelmed with journals piling up on your desk and not enough time in the day to do a targeted PubMed search, much less read all of the new hits. Along with key individuals clinical studies, the aforementioned international consensus guideline,7 as well as systematic reviews and meta-analyses, are a time-efficient way to help the clinician recognize patterns and synthesize evidence to identify answers or solutions to important research and clinical questions.8 Now, let’s explore the vitamin D-PCOS link further, from epidemiologic to intervention evidence.

THE VITAMIN D-PCOS LINK
Vitamin D status and PCOS
Systematic review of vitamin D research indicates that hypovitaminosis D (low serum 25-hydroxvitamin D [25(OH)D]) is common in women with PCOS.9 In a review of PCOS etiology, average serum 25(OH)D levels ranged 11–31 ng/mL, but the majority of patients (67%–85%) had values < 20 ng/mL,1 which is the cutoff for deficiency according to a vitamin D clinical practice guideline from the US Endocrine Society.10
Serum vitamin D status is inversely associated with PCOS symptoms and pathology, including obesity,11,12cardiovascular disease risk,13 and insulin resistance.2,11 In a clinical study investigating the impact of lifestyle intervention on health outcomes in women with overweight or obesity and PCOS, higher 25(OH)D concentrations were significantly associated with lower waist circumference and total cholesterol among participants of both cohorts.14

Taken together, these findings suggest that vitamin D status is an important therapeutic consideration for women with PCOS.

Vitamin D supplementation and PCOS
Vitamin D supplementation studies show promising results for the potential impact of this essential micronutrient in PCOS symptomology. A 2018 systematic review and meta-analysis examined 11 randomized controlled trials (RCTs) including > 600 patients with PCOS; as expected, vitamin D deficiency and insufficiency were observed to be prevalent in this patient group, and vitamin D supplementation significantly improved 25(OH)D status.15 Analyses considered factors like dose frequency and whether vitamin D supplementation was provided alone or as a co-supplement. Major findings include: continuous daily supplementation (i.e., as opposed to weekly bolus dosing) with vitamin D (< 4,000 IU/day) alone reduced homeostatic model assessment of insulin resistance (HOMA-IR). Vitamin D provided as a co-supplement (i.e., in combination with other micronutrients – vitamin K, calcium, zinc, or magnesium) also reduced HOMA-IR and also decreased fasting glucose concentrations.15 In other words, vitamin D supplementation yielded improvements in insulin sensitivity in women with PCOS.15

Biomarkers of oxidative stress and inflammation among women with PCOS have also been examined in RCTs with vitamin D intervention; overall, higher dose groups experienced improvements in oxidative stress and inflammation.16 For example, one 3-month study included in both meta-analyses15,16 investigated the impact of vitamin D supplementation with or without with metformin on metabolic profiles of insulin resistant, Iranian women with PCOS.17 This RCT randomized patients into three groups: “high dose” vitamin D (4,000 IU/d) + metformin, “low dose” vitamin D (1,000 IU/d) + metformin, or placebo + metformin. Following intervention, metabolic profiles were significantly improved in the high dose vitamin D group compared to the low dose and placebo groups.17

Specifically, the high dose vitamin D group experienced significantly lower total testosterone, lower prevalence of hirsutism, and lower high-sensitivity C-reactive protein (hs-CRP), a marker of inflammatory response.17 Additionally, significant elevations in total antioxidant capacity (showing improved free radical fighters) and sex hormone binding globulin (SHBG) were observed in the high dose vitamin D group, indicating improved body regulation of circulating hormones.17

Female-centric considerations for vitamin D status
There are many risk factors for vitamin D deficiency in women, which we have covered previously. One gender-based factor for some women, constructed by cultural and/or religious forces, may be partial or complete covering with clothing, and thus, limited exposure to sunlight and cutaneous synthesis of vitamin D.

Additionally, with the increased prevalence and public health awareness of skin cancer, more women are using sunscreen and limiting time in the sun. Because of less opportunity to receive vitamin D through the skin, clinicians should discuss the implications of low vitamin D status with their patients and promote practical ways to achieve and maintain healthy serum 25(OH)D levels– namely, vitamin D supplementation.

Genomic risk and PCOS
The actions of the active, hormone form of vitamin D [1,25(OH)2D] are mediated by the vitamin D receptor (VDR). And over 3% of the human genome is regulated by the VDR gene.18 That may not sound like a lot, but it translates into hundreds of protein-coding genes. With advances in genetic testing for various diseases, many patients may want to know if there is a genetic component to PCOS. One meta-analysis found that VDR Fokl and Taql polymorphisms were associated with an increased risk of PCOS in certain populations (e.g., Asians).18 Another meta-analysis found that VDR variants, Apal, Bsml, and Fokl, were associated with heightened risk of diseases related to insulin resistance, particularly in Caucasians with darker skin (i.e., from Saudi Arabia, India, Egypt, and Iran) and Asian populations.19

The good news is that even if the patient carries a VDR variant linked to PCOS, improving vitamin D status via lifestyle modifications (e.g., achieving healthy weight, incorporating sun exposure in moderation, and incorporating vitamin D sources in the diet) along with intervention via routine vitamin D supplementation has more impact on PCOS outcomes than genetic variations.

Dietary/nutrition considerations in PCOS
It is well recognized that lifestyle intervention is the cornerstone of treatment for patients with PCOS.20 First line PCOS treatment should include targeted lifestyle modifications that focus on weight management, including optimizing dietary approach and increasing physical activity. In fact, the good news is that a relatively low reduction in weight (~ 5 percent) can improve insulin resistance, hyperandrogenism, menstrual function, and fertility.20,21

Clinical consensus for dietary recommendations from the international consortium have focused on overall reduction in calorie intake and general healthy eating principles, with no one particular diet reported to have more favorable outcomes over another. Dietary guidelines and lifestyle recommendations are centered on achieving a healthy weight and managing metabolic and reproductive functions. The following recommendations have been shown via research to be successful nutritional management approaches for PCOS:21-24

• Hypocaloric diet with balanced intake throughout the day.21 (Note that the authors acknowledge that the caloric restriction model has many flaws, and certainly is difficult for patients to sustain. We don’t have an equally proven replacement, though intermittent fasting and the ketogenic diet hold promise.)
• Small, frequent meals; avoid skipping meals in order to stabilize blood sugars and diminish extreme hunger21,22
• Low glycemic index carbohydrates that are low in refined carbohydrates and high in fiber22
• High-protein, low-glycemic-load hypocaloric diet improves weight loss and PCOS symptomology23
• Emphasis on mono- and polyunsaturated fats, especially omega-3 fatty acids (e.g., consuming oily fish up to 4x/week)22
• Mediterranean-inspired, low-glycemic-load, anti-inflammatory diet has shown good prognostic metabolic and reproductive responses to weight loss in PCOS24
• Low carbohydrate (< 20 g) ketogenic diet is emerging area of research with promise and may be beneficial for certain patients, depending on adherence to diet restrictions25-26
• Targeted supplementation; nutrients of concern include but are not limited to vitamin D3, chromium, omega-3 fatty acids (EPA+DHA)22

More on the ketogenic diet for PCOS—initial data are promising, but not quite ready for prime time according to PCOS guidelines, though it is an active area of investigation. Other areas of active research include intermittent fasting and the fasting-mimicking diet.
Regardless of the dietary approach, “Weight loss should be targeted in all overweight women with PCOS through reducing caloric intake in the setting of adequate nutritional intake and healthy food choices irrespective of diet composition.”20

Improving vitamin D status in patients with PCOS
Individual nutrients of interest in PCOS research, such as vitamin D, were not specifically addressed in the 2018 international PCOS guidelines.6 However, because the growing body of research on vitamin D status and supplementation interventions in patients with PCOS is compelling, it is prudent for practitioners to partner with patients to assess their vitamin D status (via serum 25(OH)D concentration; sufficiency is defined as ≥ 30 ng/mL) and help them achieve and maintain vitamin D sufficiency through supplementation.10

Supplementation recommendations can be personalized based on periodic serum 25(OH)D measurements (e.g., it can take 3-4 months for 25(OH)D to reach a new steady state), and dosing depends on whether you are repleting a deficient state (6,000 IU/day or 50,000 IU/week for 8 weeks) or maintaining a 25(OH)D level in the normal range (at least 1,500-2,000 IU/day).10 However, it is important to remember that patients with overweight and obesity (common in PCOS) may need 2-3 times more vitamin D daily than their normal-weight counterparts.10

Optimal healthcare approach for patients with PCOS
A multidisciplinary, holistic, and personalized lifestyle medicine approach to care is the best practice for patients with PCOS. Collaboration and continuity of care with specialists across the PCOS spectrum has the greatest impact on outcomes and patient satisfaction.6,27

The evidence-based guidelines recommend lifestyle management as the first line therapy, with weight management being of utmost importance. Modest weight loss can net significant metabolic and hormonal improvements in patients with PCOS.20 Research indicates that weight management outcomes in women with PCOS are likely improved by the inclusion of the following factors: behavioral and psychological strategies, goal setting, self-monitoring, cognitive restructuring, problem solving, relapse prevention.28 Strategies that target improvements in motivation, social support, and psychological well-being are also key.28

Providing your patients with high-quality, multidisciplinary resources and referrals will improve their opportunity to receive support for the necessary lifestyle modifications.27 This may include consultations with fertility experts, endocrinologists, cardiologists, behavioral health specialists, registered dietitian nutritionists, or personal trainers, to name a few. Ask your patients what barriers to lifestyle management they may experience, and partner with them to champion key, gradual changes toward healing and wellness.
​
Although vitamin D supplementation recommendations are not yet included in the latest international PCOS guidelines, the evidence to date indicates that assessment and treatment of vitamin D deficiency and insufficiency among PCOS patients is likely a critical piece of the PCOS management puzzle. Vitamin D supplementation is the most pragmatic, beneficial, and clinically necessary approach when serum 25(OH)D levels are low, a scenario that applies the majority of patients with PCOS.
Citations

1. Thomson RL et al. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clin Endocrinol (Oxf). 2012;77(3):343-350.
2. Hart R. Polycystic ovarian syndrome—prognosis and treatment outcomes. Curr Opin Obstet Gynecol. 2007;19(6):529–535.
3. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997;18(6):774-800.
4. Ding T et al. The prevalence of polycystic ovary syndrome in reproductive-aged women of different ethnicity: a systematic review and meta-analysis. Oncotarget. 2017;8(56):96351-96358.
5. McCartney CR et al. Polycystic ovary syndrome. N Engl J Med. 2016;375(1):54-64.
6. El Hayek S et al. Poly cystic ovarian syndrome: an updated overview. Front Physiol. 2016;7:124.
7. Teede HJ et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018;110(3):364-79.
8. Gopalakrishnan S et al. Systematic reviews and meta-analysis: understanding the best evidence in primary healthcare. J Family Med Prim Care. 2013;2(1):9-14.
9. He C et al. Serum vitamin D levels and polycystic ovary syndrome: A systematic review and meta-analysis. Nutrients. 2015;7:4555-4577.
10. Holick MF et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930.
11. Hahn S et al. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes. 2006;114(10):577-583.
12. Yildizhan R et al. Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Arch Gynecol Obstet. 2009;280(4):559-563.
13. Talbott EO et al. Do women with polycystic ovary syndrome have an increased risk of cardiovascular disease? Review of the evidence. Minerva Ginecol. 2004;56(1):27-39.
14. Thomson RL et al. Seasonal effects on vitamin D status influence outcomes of lifestyle intervention in overweight and obese women with polycystic ovary syndrome. Fertil Steril. 2013;99(6):1779-1785.
15. Łagowska K et al. The role of vitamin D oral supplementation in insulin resistance in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2018;10(11):E1637.
16. Akbari M et al. The effects of vitamin D supplementation on biomarkers of inflammation and oxidative stress among women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Horm Metab Res. 2018;50(5):271-279.
17. Jamilian M et al. Effect of two different doses of vitamin D supplementation on metabolic profiles of insulin-resistant patients with polycystic ovary syndrome. Nutrients. 2017;9(12):E1280.
18. Deswal R et al. Unveiling the association between vitamin D receptor and poly cystic ovary syndrome – a systematic review and meta-analysis. Int J Vitam Nutr Res. 2018:1-12.
19. Han FF et al. VDR gene variation and insulin resistance related diseases. Lipids Health Dis. 2017;16(1):157.
20. Moran LJ et al. Dietary composition in the treatment of polycystic ovary syndrome: a systematic review to inform evidence-based guidelines. J Acad Nutr Diet. 2013;113(4):520-545.
21. Faghfoori Z et al. Nutritional management in women with polycystic ovary syndrome: A review study. Diabetes Metab Syndr. 2017;11 Suppl 1:S429-432.
22. Rondanelli M et al. Focus on metabolic and nutritional correlates of polycystic ovary syndrome and update on nutritional management of these critical phenomena. Arch Gynecol Obstet. 2014;290(6):1079-1092.
23. Mehrabani HH et al. Beneficial effects of a high-protein, low-glycemic-load hypocaloric diet in overweight and obese women with polycystic ovary syndrome: a randomized controlled intervention study. J Am Coll Nutr. 2012;31(2):117-125.
24. Salama AA et al. Anti-inflammatory dietary combo in overweight and obese women with polycystic ovary syndrome. N Am J Med Sci. 2015;7(7):310-316.
25. Mavropoulos JC et al. The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: a pilot study. Nutr Metab (Lond). 2005;2:35.
26. Gupta L et al. Ketogenic diet in endocrine disorders: current perspectives. J Postgrad Med. 2017;63(4):242-251.
27. Ko H et al. Analysis of the barriers and enablers to implementing lifestyle management practices for women with PCOS in Singapore. BMC Res Notes. 2016;9:311.
28. Brennan L et al. Lifestyle and behavioral management of polycystic ovary syndrome. J Womens Health (Larchmt). 2017;26(8):836-848.

Sara Gottfried, MD is a board-certified gynecologist and physician scientist. She graduated from Harvard Medical School and the Massachusetts Institute of Technology and completed residency at the University of California at San Francisco. Over the past two decades, Dr. Gottfried has seen more than 25,000 patients and specializes in identifying the underlying cause of her patients’ conditions to achieve true and lasting health transformations, not just symptom management.
Dr. Gottfried is the President of Metagenics Institute, which is dedicated to transforming healthcare by educating, inspiring, and mobilizing practitioners and patients to learn about and adopt personalized lifestyle medicine. Dr. Gottfried is a global keynote speaker who practices evidence-based integrative, precision, and Functional Medicine. She recently published a new book, Brain Body Diet, and has also authored three New York Times bestselling books: The Hormone Cure, The Hormone Reset Diet, and Younger.
Kari Hamrick, PhD, RD is a registered dietitian with over 25 years of experience in nutrition and wellness and is the founder of Navigate Nutrition and Wellness, a private practice nutrition counseling center located in Gig Harbor, WA. Dr. Hamrick earned her PhD in nutritional sciences from Texas Woman’s University and received Adult Weight and Lifestyle Management certification from the Commission on Dietetic Registration. Kari has special training and experience in Mindfulness Based Eating Awareness Training (MB-EAT), women’s health issues, and the nutritional management of heart disease, eating disorders, and digestive health. Dr. Hamrick is currently completing a medical communication fellowship at Metagenics. Dr. Hamrick’s passion is helping individuals meet their nutrition and health goals with respect, open communication, and a sense of humor. She is also a yoga and dance instructor and enjoys learning and performing aerial acrobatic arts.

​by Ashley Jordan Ferira, PhD, RDN

The importance of vitamin D in diverse organ systems and biochemical processes is ever-growing with novel research findings. From calcium absorption to extraskeletal health processes such as immune function- vitamin D is essential. 

The role of vitamin D in pain management is a newer area of investigation that has not been fully established. It is estimated that 25.3 million American adults experience pain every day, with nearly 40 million experiencing some form of extreme pain.1 Annual costs associated with treating pain and pain-related symptoms are estimated to be higher than cancer and diabetes combined, reaching upwards of $600 billion per year.2 The striking number of Americans experiencing pain, combined with the associated financial burdens, underscores the need for clinically efficacious pain management methods.

Chronic non-specific widespread pain (CWP) including fibromyalgia (FMS) is associated with diffuse pain, reduced pain threshold, multiple points of tenderness, disability, and decreased quality of life. To better understand if vitamin D supplementation can significantly impact (CWP) including fibromyalgia (FMS), researchers, performed a systematic review and meta-analysis, the results of which were published in Clinical Rheumatology.3

Researchers comprehensively assessed databases for pertinent vitamin D trials. The authors focused on randomized controlled clinical trials evaluating the effects of vitamin D on CWP and FMS; 4 clinical trials met the inclusion criteria.  After pooling the data from over 270 patients, regression, sensitivity and heterogeneity analyses were evaluated. Visual Analog Scale (VAS) of pain intensity was a major outcome measure.

Pooled results revealed a significantly lower VAS of pain intensity in CWP patients who received vitamin D treatment vs. those who received a placebo control. The analysis concluded that vitamin D supplementation decreased pain scores and improved pain symptoms.

Why is this Clinically Relevant?

• The personal quality of life and economic burdens associated with chronic pain are immense
• Supplementation of vitamin D for those with chronic widespread pain, including fibromyalgia, may help with pain management by reducing pain intensity
• Additional, well-designed trials are needed to further elucidate the roles and pathophysiological mechanisms of vitamin D in pain management; functional status indicators and quality of life improvements should be explored

Reference
Link to abstract
Citations 

1. NIH analysis shows Americans are in pain. National Institutes of Health. https://www.nih.gov/news-events/news-releases/nih-analysis-shows-americans-are-pain. Published August 12, 2015. Accessed October 5, 2017.
2. Relieving pain in America: a blueprint for transforming prevention, care, education, and research. Washington, D.C.: National Academies Press; 2011.
3. Yong WC, Sanguankeo A, Upala S. Effect of vitamin D supplementation in chronic widespread pain: a systematic review and meta-analysis. Clin Rheumatol. 2017;36(12):2825-2833.

The female-centric 411 on this essential nutrient

by Ashley Jordan Ferira, PhD, RDN
Overview
Vitamin D research and daily news headlines are ubiquitous. PubMed’s search engine contains over 81,400 articles pertaining to vitamin D.1 Information abounds on vitamin D, but the vetting and translation of that information into pragmatic recommendations is harder to find. Evidence-based takeaways and female-centric recommendations are crucial for healthcare practitioners (HCPs), their female patients and consumers alike. Women are busy, multi-tasking pros, so practical, personalized takeaways are always appreciated. In other words, women need the “411” on vitamin D. Merriam-Webster defines “411” as “relevant information” or the “skinny”.2 So for all of you busy women, here’s the skinny on vitamin D. Let’s explore common questions about this popular micronutrient.
Q: Is vitamin D more important for younger or older women?
A: All of the above. Vitamin D plays a critical role in women’s health across all life stages, from fertility/conception, to in utero, childhood, adolescence, adulthood, older adulthood, and even in palliative care. Vitamin D is converted by the liver and kidneys into its active hormone form: 1,25-dihydroxyvitamin D. This dynamic hormone binds nuclear receptors in many different organs in order to modulate gene expression related to many crucial health areas across the lifecycle, including bone, muscle, immune, cardiometabolic, brain, and pregnancy to name a few.3
Q: I am a grandmother. Are my vitamin D needs different than my daughter and granddaughter?
A: Yes, age-specific vitamin D recommendations exist. As an essential fat-soluble vitamin, women need to achieve adequate levels of vitamin D daily. Age-specific Recommended Dietary Allowances (RDA) from The Institute of Medicine (IOM),4 as well as newer clinical guidelines from The Endocrine Society,5 provide helpful clinical direction for daily vitamin D intake and/or supplementation goals.
The IOM RDAs4 are considered by many vitamin D researchers to be a conservative, minimum daily vitamin D intake estimate to support the bone health of a healthy population (i.e. prevent the manifestation of frank vitamin D deficiency as bone softening: rickets and osteomalacia):
Infants (0-1 year): 400 IU/day
Children & Adolescents (1-18 years): 600 IU/day
Adults (19-70 years): 600 IU/day
Older Adults (>70 years): 800 IU/day
The Endocrine Society’s clinical practice guidelines5 recommend higher daily vitamin D levels than the IOM, with a different end-goal: raising the serum biomarker for vitamin D status [serum 25-hydroxvitamin D: 25(OH)D] into the sufficient range (≥ 30 ng/ml) in the individual patient:
Infants (0-1 year): At least 1,000 IU/day
Children & Adolescents (1-18 years): At least 1,000 IU/day
Adults (19+ years): At least 1,500 – 2,000 IU/day
Q: I am a health-conscious woman who eats a nutritious, well-rounded diet. I should not need a vitamin D supplement, right?
A: Not so fast. Daily micronutrient needs can be met via diet alone for many vitamins and minerals. Vitamin D is one of the exceptions, which is why an alarming number of Americans (93%) are failing to consume the recommended levels from their diet alone.6-7 Very few foods are endogenous sources of animal-derived vitamin D3 (cholecalciferol) or plant-derived vitamin D2 (ergocalciferol). Some natural vitamin D sources include certain fatty fish (e.g. salmon, mackerel, sardines, cod, halibut, and tuna), fish liver oils, eggs (yolk) and certain species of UV-irradiated mushrooms.8 In the early 20th century, the US began fortifying dairy and cereals with vitamin D to help combat rickets, which was widespread. For example, one cup (8 fluid ounces) of fortified milk will contain approximately 100 IU of vitamin D.
Even though some food sources do exist, the amounts of these foods or beverages that an adult would need to consume daily in order to achieve healthy 25(OH)D levels (> 30 ng/ml) is quite unrealistic and even comical to consider. For example, you would need to toss back 20 glasses of milk daily or 50 eggs/day to achieve 2,000 IU of vitamin D! In contrast, daily vitamin D supplementation provides an easy and economical solution to consistently achieve 2,000 IU and any other specifically targeted levels.
Q: I enjoy the outdoors and get out in the sun daily, so I should be getting all of the vitamin D that I need, correct?
A: Vitamin D is a highly unique micronutrient due to its ability to be synthesized by our skin following sufficient ultraviolet (UV) B irradiation from the sun. Many factors can result in variable UV radiation exposure, including season, latitude, time of day, length of day, cloud cover, smog, skin’s melanin content, and sunscreen use. Furthermore, medical consensus advises limiting sun exposure due to its established carcinogenic effects. Interestingly, even when dietary and sun exposure are both considered, conservative estimates approximate that 1/3 of the US population still remains vitamin D insufficient or deficient.9
Q: What factors can increase my risk for being vitamin D deficient? Are there female-specific risk factors?
A: Although the cutoff levels for vitamin D sufficiency vs. deficiency are still debated amongst vitamin D researchers and clinicians, insufficiency is considered a 25(OH)D of 21-29 ng/ml, while deficiency is < 20 ng/ml.5 Therefore, hypovitaminosis D (insufficiency and deficiency, collectively) occurs when a patient’s serum 25(OH)D falls below 30 ng/ml. The goal is 30 ng/ml or higher.
Ideally, vitamin D intake recommendations4-5 and therapy are personalized by the HCP based on patient-specific information, such as baseline vitamin D status, vitamin D receptor single nucleotide polymorphisms and other pertinent risk factors.
Common risk factors for vitamin D deficiency to look out for include:
-> Overweight/obesity
-> Older age
-> Regular sunscreen use
-> Winter season
-> Frequent TV viewing
-> Dairy product exclusion
-> Darker skin (more melanin)
-> Not using vitamin D supplements
-> Malabsorption disorders (e.g. bariatric surgery, IBD, cystic fibrosis)
-> Liver disease
-> Renal insufficiency
-> Certain drug classes: weight loss, fat substitutes, bile sequestrants, anti-convulsants, anti-retrovirals, anti-tuberculosis, anti-fungals, glucocorticoids
-> Lastly, additional female-specific risk factors to look out for include exclusive breastfeeding while mother is vitamin D insufficient (can result in infant being vitamin D deficient) and certain cultural clothing that covers significant amounts of skin surface area (e.g. hijab, niqab).
Key Takeaways

• Vitamin D has gained popularity in the public due to the numerous research studies and news headlines; misinformation exists and practical recommendations are lacking
• Healthcare practitioners must be the trusted experts to translate the existing body of literature with an evidence-based and personalized approach for their patients
• Women comprise 49.6% of the world population,10 so the potential deleterious personal and public health ramifications of vitamin D deficiency are enormous
• Vitamin D plays critical skeletal and extraskeletal health support roles throughout a woman’s life. HCPs should inform patients of their age-specific vitamin D needs and how to meet them
• Vitamin D inputs from dietary and UV sources are likely insufficient to meet a woman’s daily vitamin D need consistently over time
• Vitamin D supplementation is prudent and evidence-based
• Risk factors for hypovitaminosis D are important to screen for when considering the patient’s need for a vitamin D lab test (e.g. serum 25-hydroxyvitamin D)

Citations

1. Pubmed.gov. Vitamin D. https://www.ncbi.nlm.nih.gov/pubmed/?term=vitamin+D. Accessed September 13, 2018.
2. Merriam-Webster. 411. https://www.merriam-webster.com/dictionary/411. Accessed October 6, 2017.
3. Hossein-nezhad A et al. Vitamin D for health: a global perspective. Mayo Clin Proc. 201;88(7):720-755.
4. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. National Academy Press. Washington, D.C. 2010.
5. Holick MF et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930.
6. Bailey RL et al. Estimation of total usual calcium and vitamin D intakes in the United States. J Nutr. 2010;140:817-822.
7. Fulgoni VL et al. Foods, fortificants, and supplements: where do Americans get their nutrients? J Nutr.2011;141:1847-1854.
8. Bendik I et al. Vitamin D: a critical and essential micronutrient for human health. Front Physiol. 2014;5:248.
9. Looker AC et al. Vitamin D status: United States, 2001-2006. NCHS Data Brief. 2011(59):1-8.
10. Countrymeters. World population. http://countrymeters.info/en/World. Accessed October 6, 2017.

Ashley Jordan Ferira, PhD, RDN is Manager of Medical Affairs and the Metagenics Institute, where she specializes in nutrition and medical communications and education. Dr. Ferira’s previous industry and consulting experiences span nutrition product development, education, communications, and corporate wellness. Ashley completed her bachelor’s degree at the University of Pennsylvania and PhD in Foods & Nutrition at The University of Georgia, where she researched the role of vitamin D in pediatric cardiometabolic disease risk. Dr. Ferira is a Registered Dietitian Nutritionist (RDN) and has served in leadership roles across local and statewide dietetics, academic, industry, and nonprofit sectors.

​by Ashley Jordan Ferira, PhD, RDN
A food fortification trial demonstrated that 600 IU of daily vitamin D3 had a significantly greater impact than 600 IU of daily vitamin D2 in elevating serum blood levels of 25-hydroxyvitamin D [25(OH)D].1-2
Vitamin D is essential for skeletal health and many emerging extraskeletal physiological processes, but remains one of the most common micronutrient dietary gaps, resulting in widespread hypovitaminosis D globally. Understanding how much vitamin D the body needs daily, in what form, and from what sources is still being discovered.
​
There are two forms of vitamin D: plant-based ergocalciferol (vitamin D2) and animal-based cholecalciferol (vitamin D3). D2 can be found in UV-irradiated mushrooms, certain fortified foods (breakfast cereals, margarine, and milk), dietary supplements, and vitamin D prescription medications. D3 is found in oily fish, egg yolks, fortified milk, and dietary supplements.4 Chemically, D2 and D3 are almost identical except for key side chain differences, with D2 having an additional double bond. D3 has been shown to have a higher affinity to the vitamin D binding protein, hepatic 25-hydroxylase (enzyme that converts vitamin D to the circulating 25(OH)D form) and vitamin D receptor.  Whether these chemical and cellular differences translate into differential abilities in raising serum 25(OH)D, the clinical measure of vitamin D status, has been a hotly debated topic since the early 20th century.5

Research literature to date demonstrates a robust case gaining momentum for vitamin D3 and against vitamin D2 for supplementation.4-5 In particular, a 2012 systematic review and meta-analysis by of randomized controlled vitamin D supplementation trials in humans explored a head-to-head comparison of vitamin D2 vs. D3 in raising serum 25(OH)D; vitamin D3 was clearly shown to be more efficacious at raising and maintaining serum 25(OH)D levels than vitamin D2.4 Authors concluded that vitamin D3 may be considered the preferred choice for supplementation.4

Since natural sources of vitamin D (dietary input and UVB exposure from the sun) are limited, and a daily vitamin D supplementation regimen is a personal health decision, vitamin D fortification of the food supply is an important, strategic public health measure to help increase dietary vitamin D intake and improve status in the general population.6 Clarity is needed to elucidate whether D2 and D3 are equally effective sources for food fortification, since both forms are currently utilized in the food supply.6 A study by Tripkovic et al. helps to shed light on key differences.1

Results were published in The American Journal of Clinical Nutrition by Dr. Laura Tripkovic and colleagues from a randomized, double-blind, placebo-controlled food fortification trial that included 335 healthy South Asian and white European women aged 20–64 years.1 Participants were randomized to one of five groups:
1) Placebo: Placebo juice with placebo biscuit
2) D2J: Juice supplemented with 15 mcg vitamin D2 with placebo biscuit
3) D2B: Placebo juice with biscuit supplemented with 15 mcg vitamin D2
4) D3J: Juice supplemented with 15 mcg vitamin D3 with placebo biscuit
5) D3B: Placebo juice with biscuit supplemented with 15 mcg vitamin D3

Fifteen mcg of vitamin D is equivalent to 600 IU of vitamin D, which is the US Recommended Daily Allowance (RDA) for ages 1-70 years.7 The daily food-fortified intervention was 12 weeks long during the winter, and serum total 25(OH)D levels were collected at baseline, week 6 and week 12. Data analysis combined ethnic groups.

D3-fortified consumption was shown to be twice as effective as D2 in raising 25(OH)D serum levels in the body.1 While the placebo group experienced a 25% reduction in serum 25(OH)D levels over the course of the study, the D2J and D2B groups saw 25(OH)D increases of 33% and 34%, respectively. Most effective, however, were the D3 groups, with 25(OH)D increases in the D3J and D3B groups of 75% and 74%, respectively. The D3J group induced higher incremental increases in 25(OH)D levels: 16.9 nmol/L higher than the D2J group, 16.0 nmol/L higher than the D2B group, and 42.9 nmol/L higher than the placebo group.1 Both juice- and biscuit-supplemented vitamin D3 groups demonstrated similar results, with no statistical differences seen between D3J and D3B groups.1 Compared to white European women, the South Asian women demonstrated a greater increase in 25(OH)D levels in response to both D2 and D3, which was likely caused by their lower baseline vitamin D status.1
This study shows that modest supplementation levels (600 IU daily) of D3 in food and beverage sources twice as effective at raising serum levels of 25(OH)D than vitamin D2.1This study and previous supplementation studies may impact future policy and practice for vitamin D supplementation source. Additional research addressing dose response, bioactivity of D3 versus D2 and the impact of foods with high levels of vitamin D3 is needed.2

Why is this Clinically Relevant?

• Vitamin D insufficiency and deficiency are common clinical observations; repletion via vitamin D supplementation is effective
• Vitamin D supplementation studies have previously shown vitamin D3 to be more efficacious than D2 at raising and maintaining serum 25(OH)D levels4
• Food- and beverage-fortified D3 is twice as effective as D2 in raising vitamin D serum 25(OH)D levels1 ; a relatively low dose of vitamin D (15 mcg, or 600 IU) daily over 12 weeks during the wintertime can increase serum 25(OH)D levels by clinically relevant amounts
• Government, industry and healthcare officials and practitioners should incorporate the totality of research demonstrating the superiority of vitamin D3 over vitamin D2 into their public health, product, and patient recommendations, respectively.
• For vegans preferring the plant-sourced vitamin D2 form, clinicians should consider recommending higher D2 dosing (relative to vitamin D3), likely at least 2x higher, via dietary and/or supplemental D2 sources

Link to abstract
Citations

1. Tripkovic L, Wilson LR, Hart K, et al. Daily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial. Am J Clin Nutr. 2017;106(2):481-490.
2. Medscape. Vitamin D3, Not D2, Is Key to Tackling Vitamin D Deficiency. http://www.medscape.com/viewarticle/882482#vp_1. Accessed August 18, 2017.
3. Ross AC, Taylor CL, Yaktine AL, Valle HBD. Dietary reference intakes for calcium and Vitamin D. National Academy Press. Washington, D.C. 2011.
4. Tripkovic L, Lambert H, Hart K, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. 2012;95:1357-1364.
5. Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006;84(4):694-697.
6. Wilson LR, Tripkovic L. Vitamin D deficiency as a public health issue: using vitamin D2 or vitamin D3 in future fortification strategies. Proc Nutr Soc. 2017;76(3):392-399.
7. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. National Academy Press. Washington, D.C. 2010.