by Ashley Jordan Ferira, PhD, RDN
Recent research from three well-known cohorts, The Nurses’ Health Study (NHS), NHS2 and Health Professionals’ Follow-Up Study (HPFS), reveals that higher magnesium intake is associated with lower risk of type 2 diabetes (T2D), particularly in diets with poor carbohydrate quality.1
Green leafy vegetables, unrefined whole grains, and nuts are richest in magnesium, while meats and milk contain a moderate amount.2 Refined foods, like carbohydrates (carb), are poor sources of magnesium. Diets with poor carb quality are characterized by higher glycemic index (GI), higher glycemic load (GL), and lower fiber intake. These poor carbs require a higher insulin demand.
The typical American diet is low in vegetables and whole grains, resulting in reduced magnesium intake. The Recommended Daily Allowance (RDA) for magnesium is 310-320 mg/day for adult women and 400-420 mg/day for adult men.3 Half of the US population fails to meet their daily magnesium needs, and hypomagnesemia exists in 1/3 of adults.4-5 Magnesium is needed for normal insulin signaling; current research has linked insufficient magnesium intake to prediabetes, insulin resistance and T2D.4 Increased magnesium intake has been inversely associated with T2D risk in observational studies.6
Collaborators from Tufts University, Harvard University, and Brigham and Women’s Hospital, sought to investigate the impact of magnesium intake, from both dietary and supplemental sources, on the risk of developing T2D in subjects who had diets with poor carb quality and raised GI, GL, or low fiber intake.1 They followed three large prospective cohorts, NHS, NHS2 and HPFS (totaling over 202,700 participants). Dietary intake was quantified by validated food frequency questionnaires (FFQ) every 4 years, and T2D cases were captured via questionnaires. Over 28 years of follow-up, there were 17,130 cases of T2D.
Major study findings included:1
Similar to the US population estimates, 40-50% of study participants had inadequate magnesium intake. A healthful, varied diet and supplemental magnesium (especially in diets that restrict or exclude carbohydrates, dairy or meat) are essential to ensure sufficient daily magnesium intake.
Why is this Clinically Relevant?
Link to Abstract
by Bianca Garilli, ND
Magnesium is the 4th most abundant mineral in the human body following calcium, sodium, and potassium. Intracellularly, magnesium is the 2nd most abundant cation behind only potassium.1 The number of essential roles magnesium plays in the body is extraordinary, with over 300 enzymes requiring magnesium as a co-factor for proper functioning.1
This essential element is involved in numerous critical physiological processes such as energy production (ATP metabolism, oxidative phosphorylation, and glycolysis), protein synthesis, muscle contraction, nerve function, blood glucose control, hormone receptor binding, blood pressure regulation, trans membrane ion flux, gating of calcium channels, cardiac excitability, and synthesis of nucleic acids (RNA and DNA).1
Unfortunately, magnesium is one of the most prevalent nutrient gaps in the US. The 2015 Dietary Guidelines Advisory Committee noted a substandard intake of magnesium as compared to the Estimated Average Requirement (EAR), which is the Dietary Reference Intake (DRI) used to assess population sufficiency vs. insufficiency for nutrients.2-3 A 2016 publication in Advanced Nutrition concluded, “Approximately 50% of Americans consume less than the EAR for magnesium, and some age groups consume substantially less”.4 This is especially concerning when one considers the critical implications of long-term, frequently unrecognized magnesium deficiencies.
Deficiencies in magnesium can present with overt clinical manifestations such as nausea, vomiting, lethargy, weakness, personality changes, tetany and tremor, seizures, arrhythmia, and muscle fasciculations.5 In other cases, sub clinical deficiencies may be more difficult to recognize yet have equally serious effects if left untreated. Health concerns and disease processes resulting from an underlying, subclinical magnesium deficiency may contribute to low bone mineral density and cardio-metabolic implications such as metabolic syndrome, hypertension, arrhythmia, arterial calcification, atherosclerosis, heart failure, and increased risk for thrombosis.6
A sub clinical magnesium deficiency can also disrupt sleep and cause muscle cramping, two common symptoms often glossed over but which can be signs of a bigger problem if left untreated. The impact of magnesium on these two clinical manifestations will be explored further:
Magnesium and sleep
A double-blind randomized clinical trial composed of 43 elderly participants between 60-75 years of age with diagnosed insomnia was conducted.7 The experimental group was given 500 mg/day of elemental magnesium for 8 weeks (250 mg elemental magnesium from 414 mg of Mg oxide, twice daily), while the control group received a placebo for the same length of time.7 A statistically significant increase was seen in sleep time, sleep efficiency, and concentration of serum renin and melatonin, as well as a significant decrease in insomnia severity index (ISI) score, sleep onset latency, and serum cortisol level.7
For many individuals, sleep is disrupted by restless leg syndrome (RLS) or periodic limb movements (PLMS).8 A study supplementing 12.4mmol of oral magnesium in the evenings for 4-6 weeks found that the overall sleep efficiency improved from 75 to 85%.9 The Mg-supplemented group also experienced a significant reduction in PLMS associated with arousal (7 PLMS/hr vs. 17 PLMS/hr at baseline).9
Magnesium and muscle cramps
Muscle cramping is a common occurrence among women during pregnancy, in athletes, and in the elderly, for which magnesium is often recommended.10 There are only a few studies, however, that have reviewed the efficacy of magnesium for muscle cramping.10 In a Cochrane review, 7 trials (5 parallel, 2 cross-over design) were included, with 3 of these trials studying pregnancy-associated leg cramps in 202 females and 4 trials looking at idiopathic leg cramps in 322 participants.10 Results from the studies noted no significant improvement of muscle cramping in older adults, while results in pregnancy were mixed leading the authors to recommend further studies in this population.10 The authors of a review article in Scientifica note that the mixed findings may be explained by the potential that, “deficiencies of other elemental nutrients including calcium and potassium have also been implicated in muscle cramps and spasms. It may be that magnesium is potentially helpful in situations of magnesium deficiency but is not of use if the problem is related to deficiency of another nutrient.”1
Magnesium: Daily needs and sources
Magnesium is an essential macro-mineral required by the human body. The prevalence of deficiency from serum measurements ranges from 12.5-20% of the population.11 Due to the necessity of this cation for over 300 reactions in the human body and the high risk of deficiency, magnesium levels should be routinely monitored either through blood testing and/or a diet diary review. If found to be low, magnesium stores can be replaced through increasing daily intake of the mineral through nutrition as well as routine supplementation.
Foods groups high in magnesium content include green leafy vegetables, legumes, nuts, seeds, and whole grains.12 Specific foods with high magnesium levels include spinach, Swiss chard, beet greens, turnip greens, pumpkin seeds, summer squash, soybeans, sesame seeds, quinoa, black beans, cashews, sunflower seeds, brown rice and pinto beans.12
The Recommended Dietary Allowance (RDA) for magnesium varies by age, sex, and whether pregnant or lactating:13
*RDA not able to be determined; Adequate Intake (AI) reported
Supplementation with high-quality magnesium is another, targeted way to reach optimal levels and fill dietary gaps. Supplementation dosing and form can be personalized and taken orally via capsules, tablets, liquid, and even powder. Some of the different forms available in the market include Mg oxide, gluconate, chloride, citrate, sulfate, glycinate, and L-threonate.
Bianca Garilli, ND
Dr. Garilli is a former US Marine turned Naturopathic Doctor (ND). She works in private practice in Northern California as well as running a consulting company working with leaders in the natural and functional medicine world such as the Institute for Functional Medicine and Metagenics. She is passionate about optimizing health and wellness in individuals, families, companies and communities- one lifestyle change at a time. Dr. Garilli has been on staff at the University of California Irvine, Susan Samueli Center for Integrative Medicine and is faculty at Hawthorn University. She is the creator of the Veterans for Health Initiative and is the current President of the Children’s Heart Foundation, CA Chapter.
At grocery stores across America, more and more people are choosing to buy organic produce. Why? The answer is simple: pesticides. Tests conducted by the US Department of Agriculture showed nearly 70 percent of 48 conventionally grown produce samples to be contaminated with pesticides. Even more frightening is the total of 178 different pesticides found on the thousands of products sampled by the USDA—often present even after the produce was washed.1
Although higher prices may deter you from buying organic, there’s even more frightening information about conventionally grown fruits and vegetables that may change your mind.
Your Choices Matter
A 2015 study found that people who mostly or exclusively buy organic foods had a significantly lower level of pesticides in their urine samples—in spite of the fact that they eat 70 percent more servings of fruits and veggies every day compared to adults who rarely (or never) buy organic.2 And according to several long-term studies, the dangers of pesticides appear to be amplified for children whose brain and nervous system development may be impaired by prolonged exposure.3-5 The fact is, your everyday choices really do make a difference!
The Dirty Dozen
It may seem overwhelming to make the organic switch, but due to the amount of research available on pesticide contamination, it doesn’t have to be. There are 12 specific foods you should always purchase organic whenever possible, a.k.a. the Dirty Dozen:
Because more than 90 percent of samples tested positive for the presence of at least one pesticide, these foods have been singled out for containing the highest amounts of pesticide residue. Look for the USDA sticker whenever you shop for these to help you avoid exposure.
The Clean Fifteen
Buying organic may not always be attainable. Fortunately, there’s also a group of foods called the “Clean Fifteen,” which make the cut for containing a relatively low concentration of pesticide residue:
Some of these foods, when tested, contained no pesticides whatsoever! If you can’t always buy organic, these are the safest kinds of conventional produce—for both your health and your budget.
Take Care of You
Eating organic produce is well worth it when you consider the downside to conventionally grown produce that is, more often than not, completely contaminated with harmful pesticides. By choosing organic when you buy anything off the Dirty Dozen list, you’ll make a small change that can lead to monumental improvements in your health.
For more information and access to both annual lists, visit the Environmental Working Group website.
Submitted by the Metagenics Marketing Team
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
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.
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?
Link to abstract
The female-centric 411 on this essential nutrient
by Ashley Jordan Ferira, PhD, RDN
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:
-> 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).
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.
Food-Fortified Vitamin D3 More Effective than D2 at Raising Serum 25(OH)D Levels | Blog | Metagenics
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?
by Ashley Jordan Ferira, PhD, RDN
Vitamin D is essential- it helps absorb calcium, supports nervous and muscle tissue, and the immune system. Compared to normal-weight counterparts, vitamin D deficiency is more prevalent in those with obesity. In the US over one-third of adults meet obesity criteria.1
A study in The Journal of Clinical Endocrinology and Metabolism2 examined cellular mechanisms of vitamin D trafficking in metabolically dysfunctional adipose tissue as compared to normal adipocytes in conjunction with a vitamin D supplementation intervention in a randomized, controlled trial.
Ninety-seven male subjects completed the vitamin D intervention study. Fifty-four normal-weight and 67 obese males were initially randomized to receive either 50 mcg/week of 25-hydroxyvitamin-D3 [25(OH)D3] (2,000 IU/week equivalent) or 150 mcg/week of vitamin D3 (6,000 IU/week equivalent) for one year. Vitamin D sufficiency was defined as a 25(OH)D blood level > 20 ng/ml. This serum concentration is aligned with the National Academy of Medicine’s cutoff for vitamin D sufficiency.3
Vitamin D uptake, conversion and release were investigated in control (non-insulin-resistant) and insulin-resistant 3T3-L1 adipocytes, as well as in subcutaneous adipose tissue (SAT) samples from lean and obese participants. The release of vitamin D and its metabolites were induced with the addition of adrenaline. Expression of the vitamin D receptor and vitamin D conversion enzymes, 25-hyroxylase and 1α-hydroxylase, was also examined.
The research team elucidated key differences in cellular vitamin D trafficking effects and supplementation effects:
Why is this Clinically Relevant?
Link to Abstract
by Ashley Jordan Ferira, PhD, RDN
Autism spectrum disorder (ASD) is a complex neurodevelopmental syndrome with significant social, communication and behavioral deficits and challenges.1 No cure exists for ASD, although early interventions (birth to 3 years) can yield developmental improvements.1 ASD impacts approximately 1 in 68 children in the US and is 4.5 times more common in boys (1 in 42) than girls (1 in 189).2
Vitamin D’s extraskeletal roles are numerous, including its role as a neurosteroid, impacting both brain development and connectivity, and likely synaptic plasticity as well.3 Vitamin D is also one of the most common micronutrient deficiencies. Previous research has revealed associations between gestational and early childhood vitamin D insufficiency and ASD.4 This suggests that hypovitaminosis D represents a modifiable risk factor for ASD.4Furthermore, preliminary evidence demonstrates that gene variants related to vitamin D metabolism play a role in the pathophysiology of ASD.5 Robustly designed intervention trials have been scant.
The first double-blind randomized controlled trial (RCT) utilizing vitamin D3 supplementation in children with ASD was published in The Journal of Child Psychology and Psychiatry in 2018.6 The study included 109 Egyptian children (85 boys; 24 girls) 3-10 years of age with confirmed ASD diagnosis. The children were randomized to receive vitamin D3drops (300 IU D3/kg/day; not to exceed 5,000 IU/day) or matching placebo drops daily for 4 months.6 Serum 25-hydroxyvitamin D (25[OH]D) levels were measured at baseline and 4-months. For ethical reasons, children who were identified to have vitamin D deficiency (25[OH]D <20ng/mL) were excluded from the study and administered vitamin D supplementation by the study authors.6 Autism symptoms were assessed using validated measures completed by two different psychologists and a senior psychiatrist.6
Four months of daily vitamin D3 supplementation at 300 IU/kg/day:6
Following 4 months of vitamin D3 supplementation, improvements (all p <0.05, most p <0.01; as compared to placebo) were demonstrated in many core manifestations of ASD, including:6
This rigorously designed RCT is the first of its kind to demonstrate safety and efficacy of vitamin D3supplementation in children with ASD.6 Two previous open-label vitamin D3 supplementation studies also demonstrated improvements in ASD symptoms.7-8 Wide-scale studies are warranted to continue to critically ascertain the effects of vitamin D on ASD.
Why is this Clinically Relevant?
Link to Article
Food first, but fill the gap: The case for vitamin D supplementation
Ashley Jordan Ferira, PhD, RDN
If you can have a favorite nutrient, mine would be vitamin D.
Historically famous for its essential, classical role in calcium and phosphorus homeostasis and bone physiology (think rickets prevention), the past few decades of research have unveiled diverse, extraskeletal health roles for vitamin D, including but not limited to the immune system, cardiometabolic pathophysiology, cancer, pregnancy, etc.
Whether consuming vitamin D2 or D3 (FYI, the latter more potently impacts vitamin D status),1 vitamin D ultimately circulates in the 25-hydroxyvitamin D [25(OH)D] form (the clinical biomarker used to measure vitamin D status) and acts throughout the body as a pleiotropic hormone in its active form, 1,25-dihydroxyvitamin D [1,25(OH)2D].
Unlike other nutrients, this fat-soluble vitamin is obtainable via several unique routes: the skin with adequate UVB exposure, a handful of natural food sources, a few fortified foods, dietary supplements, and even prescription drugs.
The problem is that few foods naturally contain vitamin D (e.g., egg yolk, certain fatty fish, fish liver oil, and certain species of UV-irradiated mushrooms), and fortified foods offer relatively small amounts (e.g., 100 IU vitamin D per 8 oz cup of fortified milk or orange juice),2 so vitamin D supplementation becomes a strategic solution. In the eloquent words of pediatrician and vitamin D researcher, Carol Wagner, MD: “Something so simple- vitamin D supplementation- could improve the health status of millions and so becomes an elegant solution to many of our health problems today.”
If it’s possible to be defensive of a micronutrient, I am protective of vitamin D. Non-evidence-based rumors and negative media attention targeting vitamin D are common. Some of the misinformation is hype from anti-supplement camps who make broad, sweeping statements that lack scientific substantiation. But not all of the vitamin D myths originate from bias or lack of intellectual rigor. After all, who has time to keep up with the impressive, daily output of new vitamin D research? Clinicians certainly do not have the luxury of time, not in the current healthcare paradigm. Nevertheless, when inaccurate conclusions are propagated to patients about vitamin D and their health, that’s more harm than good. So, let me help out.
This blog series explores some of the most common vitamin D myths. Let’s tackle just 1 myth today:
Myth: I get enough vitamin D from food, so I don’t need a vitamin D supplement.
Can you meet your vitamin D needs from food alone? Well, that depends on how you define “needs.” Let’s talk about the 2 major (and quite different) sets of vitamin D recommendations.
First, the National Academy of Medicine (NAM), formerly known as the Institute of Medicine, provided vitamin D Recommended Dietary Allowances (RDAs) in 2010.3 Here’s how much vitamin D NAM says that we (Americans and Canadians) need based on bone health research (think rickets and osteomalacia prevention, calcium absorption, etc.):3
But I have a bone to pick (pun intended) with NAM’s vitamin D recommendations. I find them to be problematic, if not contradictory at times, for a few key reasons.
To start with, the RDA is by definition “the average daily level of intake sufficient to meet the nutrient requirements of nearly all (97-98%) healthy people.”4 Well, that misses the unhealthy people. Since 2/3rd of the country are overweight or obese5 and heart disease and cancer are the #1 and #2 causes of mortality in the US, respectively,6 one can extrapolate that the vitamin D RDAs do not apply to a decent chunk of the gen pop.
In fact, research indicates that overweight and obese individuals require more vitamin D than their lean counterparts,7 but the NAM recommendations fail to consider adiposity.
Second, lumping a toddler and 68-year-old grandmother in the same RDA category (i.e., ages 1-70 years) seems to lack nuance. Skeletal health is critical throughout life, but you cannot tell me that the vitamin D needs for the rapidly accruing skeleton in childhood and adolescence are no different than an adult or older adult’s skeletal needs.
Third, the RDAs for daily vitamin D intake are simply incongruent with the serum 25(OH)D cutoffs NAM also published in 2010. They provided the following 25(OH)D ranges:
The somewhat ironic problem is that the overly conservative vitamin D RDAs won’t get you into the 25(OH)D range that NAM defines for sufficiency. Regular UVB sun exposure (with adequate skin surface area, right latitude, right time of year, etc.) can raise serum D levels into sufficiency, except cutaneous vitamin D synthesis from sun is highly variable and limited for many. But 400-800 IU/day of vitamin D simply won’t do the trick. It’s like asking someone to fill up an 30-gallon fish tank and giving them a few cups of water to do the trick.
In the sage words of the late Bob Heaney, MD: “We’ve been able to show that the (vitamin D) RDA barely budges the blood 25-hydroxyvitamin D level.”8 Thanks to Dr. Heaney, who made invaluable research contributions to the field of vitamin D, we know that 100 IU/day of vitamin D increases serum 25(OH)D concentrations by approximately 1 ng/mL.9That means that 1,000 IU/day of vitamin D would raise 25(OH)D by about 10 ng/mL. Although weight status, age, and the patient’s baseline vitamin D status can variably impact the supplementation response, this “rule of thumb” can be used to roughly calculate vitamin D supplementation needs.
For example, let’s take a patient: me. I have limited UVB sun exposure and consume some foods that contain vitamin D (e.g., milk, eggs, salmon) but irregularly. My daily 5,000 IU vitamin D3 supplement has my serum 25(OH)D at 54 ng/mL. It stays between 50-60 ng/mL, which is in the sufficient range.
But I’m an anomaly. Nationally representative research backs up the fact that Americans are not getting adequate vitamin D from their diets.10-11 First, 93% of Americans 2 years and older are failing to consume at least 400 IU/day of vitamin D from diet alone, and this estimate includes fortified food sources.10 Even when diet plus sun exposure are both thrown into the mix, about 1/3rd of the US population has serum 25(OH)D levels associated with vitamin D insufficiency or deficiency.11 For more details on vitamin D deficiency and why it persists, check out this blog.
Dietitians (I am one) and other clinicians love to preach “food first.” That slogan is true but ignores research on key nutrient gaps. I prefer to say, “food first, then fill the gaps.” And in the case of vitamin D, the gap is practically guaranteed, except for the outlier patient who’s knocking back fish liver oils and irradiated mushrooms.
Lastly, a more current and scientifically and clinically nuanced set of guidelines exist. One year after the NAM recommendations were released, several of the world’s leading vitamin D researchers convened to review the evidence to date, resulting in the 2011 publication: Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline.12
The US Endocrine Society’s conclusions are harmonious with the mindset of a clinician, who is tasked with addressing the vitamin D needs of unique patients. The guideline recommends higher daily vitamin D levels than NAM, with a different and logical purpose in mind: Raising serum 25(OH)D levels into the sufficient range (≥ 30 ng/ml):12
The guidelines even differentiate vitamin D needs based on adiposity: Children and adults who are obese may need 2-3 times more vitamin D daily than normal-weight individuals.12 Finally, the US Endocrine Society provides clear guidance for correcting vitamin D deficiency in all age groups, with repletion and maintenance dosing information, which is a topic that I will cover in a future blog.
Individual genetic differences for the vitamin D receptor (VDR) (i.e., gene polymorphisms like Cdx2, Apa1, Fok1, Taq1) are another important facet to weave into each patient’s unique vitamin D story, underscoring the prudence of a personalized lifestyle medicine approach to treat the individual.
No, you cannot satisfy your vitamin D needs from food alone. If you plan to raise and maintain your serum 25(OH)D level (the biomarker that indicates vitamin D status) in the sufficient range for skeletal and extraskeletal health, that will require daily vitamin D supplementation. Remember, 30 ng/mL is not the goal. It’s the cutoff for insufficiency.
Here’s a sneak peak at some of the additional vitamin D myths that will be covered in future blogs:
Do you have a question about the science and clinical application for vitamin D? Let me know by commenting below!
Ashley Jordan Ferira, PhD, RDN is Manager of Medical Affairs and 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.