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599254720Heartburn, often called acid indigestion is when there is a burning/acidic sensation in the chest. It is caused by a back up of acid from the stomach into the esophagus and throat. Classic symptoms are those burning sensation behind the sternum and/or in the throat, but can also be accompanied by nausea, belching, bloating. When we have one or more of these symptoms, it may not be a simply case of heartburn, which is a symptom, but rather gastroesophageal reflux disease (GERD), which is a disease that involves chronic acid regurgitation that can damage the lining of the esophagus. If one has at least two episodes of heartburn per week, that is when we need medical advice and perhaps an evaluation for GERD. GERD can also exist without any heartburn/acidic sensation at all…but perhaps a nagging cough, hoarseness, laryngitis, wheezing, postnasal drip, sinusitis, chest/ear or jaw pain, painful swallowing or a sensation in the throat.

There are natural medicine supplements, over the counter pharmaceuticals and prescription medications for heartburn and GERD. What I want to focus on here though, are the basic lifestyle changes that are fundamental to any pill, no matter the nature of the pill.

· WEIGHT-Weight management- excess weight, especially abdominal fat can contribute to heartburn or GER by putting pressure on the stomach which then pushes the contents up into the stomach. Even a gain of 10 # in women can increase the risk by 40%. Once a woman is in the category of overweight or obese, the risk of GERD symptoms doubles or triples. Losing weight can decrease symptoms.

· TIMING OF EATING-Avoid eating for 2-3 hours before bedtime. This allows time for the stomach to empty. Even before going to bed, avoid lying down after eating and avoid exercising right after eating.

· SMALLER MEALS; REDUCE FLUIDS WITH MEALS-Larger meals puts greater pressure on the lower sphincter of the stomach which then leads to a greater likelihood of back up into the esophagus.

· STOP SMOKING- Smokers have an increased risk for acid reflux due to possible relaxing effects of the smoking on the sphincter. Smoking also decreases salivary production and with less saliva, we miss out on some neutralization of acid in the stomach.

· AVOID SELECT FOODS and BEVERAGES- Spicy, fatty foods, fried foods, citrus fruits and beverages, alcohol, chocolate, milk, peppermint, coffee, tea, carbonated beverages and milk. Some relax the sphincter, some are acidic and some actually promote acid production.

· ELEVATE THE HEAD OF YOUR BED-for those who have symptoms at night or early in the morning, putting wooden blocks under the headboard to raise it 4-8 inches can help to prevent reflux. Another option is to use a foam bed wedge which elevates the upper part of the body.

· SLEEP ON LEFT SIDE- believe it or not… this could help… Our stomach bends to the left… so when you lie on the left side, a portion of the stomach is lower than the esophagus… which may help to reduce backup of food and acid into the esophagus. Every little bit can help.

· SUGARLESS GUM-chewing gum after meals can stimulate saliva production which then helps to neutralize stomach acid and soothe the lining of the esophagus. I would also mention here to choose gum wisely in terms of healthier choices for the gums and teeth. One example includes those made with xylitol.

· CHECK MEDICATIONS-some medications can actually cause or contribute to heartburn or acid reflux. Your doctor and pharmacist can be very helpful here. Possible suspects include bisphosphonates, aspirin, ibuprofen, benzodiazepines, opioid narcotics, calcium channel blockers, potassium, progestins, certain antihistamines and antispasmodics, and even peppermint based herbal products.

· AVOID TIGHT CLOTHES-tight pants at the waist, tight girdles and belts can put pressure on the stomach and can worsen reflux.

· BEND AT THE KNEES- there are many reasons to bend at the knees when lifting or picking up items from the floor due to low back care in particular… but for those individuals who may do this repetitively due to their job or activities of daily living… this may also put pressure on the stomach.

That’s it for now, in terms of lifestyle changes that serve as the basic foundation upon which to add select nutritional/botanical supplements that address both cause and provide symptom relief or over the counter or prescription medications if needed.

488559207Did you know that curcumin, a component of turmeric (Curcuma longa), has antidepressant activity? Natural medicine has much to offer individuals who suffer from mild to moderate depression, and increasingly, we have things to offer for those with major depression. One of the problems with conventional treatments, is that nearly 50% of patients with major depressive disorders discontinue their medication due to side effects. Finding treatments that do not cause side effects, then becomes much needed area of optimal management. Curcumin, a component of turmeric rhizome has been studied in several clinical trials, but the current paper is a meta-analysis the evaluated the safety and effectiveness of curcumin in treating major depressive disorder.

The meta-analysis of the literature that was searched included those that met the following criteria: (1) human study, (2) quantitative analysis, (3) intervention and control group, (4) curcumin was an independent intervention, (5) study addressed only major depressive disorder, (6) depression was measured with standardized scales, and (7) the study was in English. Studies were also rated according to quality and the data from all the studies were converted into Hamilton Depression Rating Scale scores.

A total of 1757 studies were identified, and six met all the inclusion criteria which totaled 342 patients (n=177 curcumin and n=165 control). There were four randomized controlled trials, one crossover study, and one open-label study. All patients received an antidepressant prescription medication in addition to either curcumin (1 g/day, n = 5 studies or 500 mg/day, n = 1 study) or placebo. Five of the studies rated strong in quality and one was moderate.

In this meta-analysis there was a significant reduction in major depressive symptoms with curcumin treatment compared with control. In addition, several subgroup analyses demonstrated that curcumin had a significant benefit in middle-aged patients but not older-aged patients, although age ranges were not defined; curcumin had a significant benefit in patients treated for > 6 weeks but not in patients treated for < 6 weeks; 500 mg / day of curcumin did not have an effect but 1,000 m g/day did have a significant benefit; and curcumin had a significantly greater benefit in those patients who only had major depressive disorder vs. those with major depressive disorder and other chronic health problems.


This appears to be the first meta-analysis of the effect of curcumin on major depressive disorder. Summary conclusions are that curcumin is effective in reducing symptoms of depression in patients with major depressive disorder and are already taking prescription antidepressants, and that curcumin is more effective in middle-aged patients. Effective doses were 1 g/day for > 6 weeks. A few cautionary notes with this meta-analysis are that there were only 6 studies; only two doses of curcumin were evaluated; the piperine used to enhance curcumin and/or the doses of curcumin may not have been optimal and that the study was quite short term for such a chronic condition. On the other hand, the methodology the authors used was rigorous and I am encouraged by the research on curcumin and depression.

Reference: Al-Karawi D, Al Mamoori DA, Tayyar Y. The role of curcumin administration in patients with major depressive disorder: Mini meta-analysis of clinical trials. Phytother Res. 2016;30(2):175-183.

Fenugreek seed has a long tradition of being used as an a466762923gent to increase the production of breast milk (“galactagogue”). There is general agreement among health care advisory organizations, including the World Health Organization, breast feeding is recommended for at least 6 months, due to its short and long term health benefits to the recipient. Not all women have sufficient milk production to succeed in a 6-month duration, and simple, safe methods are welcome options. The goal of this randomized, controlled, double-blind, clinical trial was to evaluate the effect of a fenugreek seed herbal tea on the signs of breast milk sufficiency in female infants from birth to the age of 4 months.

The study was conducted in Tehran, Iran and included 78 healthy female infants and their mothers. The infants weighed between 5.5 and 8.8 lbs., had normal sucking ability, were not consuming infant formula or other sources of nourishment. No other herbal or pharmaceutical agents were being used by the women to promote lactation.

The lactating women were randomly assigned to receive an herbal tea containing 7.5 g fenugreek seed powder in addition to 3 g black tea powder (n=39) or to the control group that was an herbal tea containing 3 g black tea powder (n=39). Teas were consumed 3 times per day, 2 hours after each meal for 4 weeks.

Growth measurements included infant weight, height, and head circumference and were done at baseline and each weekly visit. Mothers completed questionnaires about demographic factors and breastfeeding conditions and completed a 2-day account of the number of daily wet diapers, frequency of infant defecation, and the number of times they breast fed each day.

Upon entry into the study, women in both groups had similar body mass index, age, and similar infant weight, height, or head circumference.

After 4 weeks of teas: weight, head circumference, number of wet diapers, frequency of defecation, and number of breastfeeding times increased significantly in the fenugreek group compared with baseline. The growth in infant height was not different between the two groups. Growth in height difference between the 2 groups was not significant.

Commentary: While this was a small study, and the use of fenugreek teas was used in conjunction with black tea, it appears that fenugreek seed did improve signs of breast milk sufficiency. It would have been useful to know how much fenugreek seed was in the tea, how the tea was prepared as we do not know if it was an infusion or a decoction or even just mixing the powder into hot water and instantly drinking. It would also be useful to know how much liquid was consumed in each unknown amount of tea. I would also want to know if this approach could help a woman reach the goal of 6 months of lactation. All of that said, this study in my view, supports the tradition of fenugreek in promoting milk supply in lactating women, and supports the usefulness of it in women who want to assure the delivery of adequate milk to their infants.


Ghasemi V, Kheirkhah M, Vahedi M. The effect of herbal tea containing fenugreek seed on the signs of breast milk sufficiency in Iranian girl infants. Iran Red Crescent Med J. August 15, 2015;17(8):e21848. doi: 10.5812/ircmj.21848.

185081880Premenstrual syndrome (PMS) includes one or more of many symptoms in the areas of mood, the physical body and cognition. The most frequent symptoms are irritability, depression, fatigue, water retention, weight gain, breast tenderness, headaches, abdominal cramps and mood swings. About 80% of women may experience PMS and about 50% of women seek medical care for their symptoms.

The primary etiology of PMS has been thought to be the interplay of serotonin and hormones which is why conventional treatment of PMS most often includes SSRIs to increase serotonin levels and/or birth control pills to suppress ovarian hormone secretion.

High sensitivity C-reactive protein (hs-CRP) is an acute phase inflammatory marker that has been associated with risk for cardiovascular disease and menopausal hot flash symptoms. It has also been associated with some of the risk factors for PMS including depression, smoking, increased body mass index (BMI) and aging. Some studies have investigated the role of inflammation and PMS but only suggestive not significant connections have been observed. Select anti-inflammatory medications can also provide relief for some PMS symptoms.

The current study used data on PMS symptoms from a much larger study called the Study of Women’s Health Across the Nation (SWAN), a racially and ethnically diverse study of midlife women from five racial/ethnic groups and at seven clinical sites nationwide. The goal was to determine if hs-CRP was associated with PMS. The proportion of women who reported each PMS symptom, except breast pain or headaches, was significantly increased (26%-41%) for women who had hs-CRP values > 3 mg/L. A hs-CRP level > 3 mg/L in women with PMS was associated with mood symptoms, abdominal cramps, back pain, appetite cravings, weight gain, and bloating, but not with headaches, breast pain for women with three or more PMS symptoms.

Most symptoms, except for headaches and breast pain were reported by significantly more obese women, women who smoked or were exposed to passive smoke and by women with an elevation of depressive symptom scores.

Commentary: There has been very little literature that has focused on any relationship between inflammation and PMS. The current study that does observe a significant relationship with at least some PMS symptoms and in women who have less than 3 PMS symptoms suggests that inflammation may be involved in PMS. That said, I would not abandon the serotonin-hormone connection and would continue to recognize that PMS is likely a complex disorder with potentially different mechanisms for the etiologies of at least some of the symptoms. In addition to biology, there are numerous social, demographic and behavioral factors that are likely associated with PMS. The lifestyle and natural agents that have published research support that I rely on the most in clinical practice are aerobic exercise 4 or more times per week, St John’s wort, calcium, vitamin B6, chaste tree, magnesium, vitamin E and borage seed or evening primrose oil. For more difficult mood disorder PMS patients, usually called premenstrual dysphoric disorder (PMDD), I add one or more of the following: tryptophan, theanine, lavender, GABA, SAMe and more.


Ellen B. Gold, PhD, Craig Wells, BA, and Marianne O’Neill Rasor, MA. The Association of inflammation with premenstrual syndrome. J Women’s Health 2016; May on line ahead of print

Polycystic ovarian syndrome (PCOS) is a common endocrine problem that is486352462 diagnosed in reproductive aged women. It’s complex and involves multiple body systems but is associated with hyperinsulinemia, impaired glucose metabolism, hyperandrogenism and dyslipidemia. It is estimated that 5-6 million women in the United States have PCOS. The manifestations of PCOS can include irregular/infrequent menses or no menses at all, infertility, polycystic ovaries, abnormal hair growth (hirsutism), hair thinning, acne, weight gain and in time, an increased risk for type 2 diabetes, cardiovascular disease and endometrial cancer.

PCOS is a strong area for natural medicine that includes good science on nutrition, exercise, N-acetyl cysteine, myo-inositol, d-chiro-inositol, cinnamon, spearmint, licorice, fish oils and more.

The current study compared women who received a soy isoflavone supplement for 12 weeks with placebo. The study enrolled 70 women between the ages of 18 to 40, and who met the diagnostic criteria, called the Rotterdam criteria, for a diagnosis of PCOS. Women were given either a 50 mg soy isoflavone capsule per day or a placebo daily, for 12 weeks. All women also took metformin at 500mg/day which was increased to 1,500 mg/day. One of the uses of metformin is to improve insulin sensitivity which in women with PCOS, hopefully leads to lowered androgens and regular ovulation with regular menses. No other dietary supplements were allowed.

The women who took the soy isoflavone supplement had significantly improved insulin resistance (measured by a decrease in serum insulin levels and two other important tests that measure insulin resistance and insulin sensitivity called the HOMA-IR and the QUICK1), as well as improvement in androgen levels and triglycerides.

Commentary: Soy foods in the diet of women with PCOS have been a staple of my nutritional advice for women with PCOS, due to other evidence that soy phytoestrogens can improve lipids and lower some of the free testosterone. I would not be inclined to just rely on a soy isoflavone supplement or soy foods to fully address PCOS, but in terms of medicinal foods, soy foods and/or a soy isoflavone supplement is an important dietary influence for women with PCOS. Do not be misled by the term “phytoestrogen”, some of the natural compounds in soy. Soy does not contain estrogen nor does it increase estrogen levels, nor does it cause hormonal cancers.


Jamilian M, Asemi A.  The effects of soy isoflavones on metabolic status of patients with polycystic ovarian syndrome.   J Clinical Endocrinology and Metabolism. 2016, August, first published online

494150385Migraines are chronic and debilitating and affect 12-20% of the world’s population, and are more common in women. Women account for about three quarters of the 28 million Americans who experience migraine headaches. Attacks can begin at any age, but they typically start during childhood or adolescence when they are pretty equal in boys and girls. By early adolescence though, the prevalence becomes more dominant in women. This prevalence of migraines peaks in women in their early forties, and then declines steadily as we age, but may not resolve completely. Migraines tend to reduce in frequency in postmenopausal women, with estrogen levels decreasing significantly and also stabilizing without monthly fluctuations.

Only about half of patients achieve a 50% reduction in the frequency of their attacks, despite the availability of prophylaxis options. Sadly, only 3-5% of chronic migraine sufferers receive adequate prophylaxis therapy.

A randomized, multi-center, parallel-group design was conducted in which melatonin was compared with amitriptyline and placebo for 12 weeks. Patients were randomized into one of three groups: placebo, melatonin 3 mg or amitriptyline 25 mg before bed, daily. After a 4-week baseline phase, 196 patients were randomized with 65 in the placebo group, 66 received amitriptyline and 65 received melatonin. Those numbers in each group decreased slightly as 18 were lost to follow-up.

Patients were men and women ages 18-65 and had migraines with or without aura for at least 1 year and first onset prior to age 50 years. Patients were included in the study if they had at least three migraine headache attacks or four migraine headache days (a headache of at least 30 minutes in duration) per month but < 15 headache attacks over month during each of the previous 3 months prior to the screening visit. Patients were excluded if they had a past or present psychiatric disorder, used ergotamine, triptan medications, opioid or combinations of those for > 10 days per month or just an analgesic for > 15 days/month for > 3 months. They were also excluded if they were unable to discontinue their prophylactic medications, or had previously taken melatonin, amitriptyline or agomelatine or had uncontrolled hypertension at the screening visit or at randomization.

Mean headache frequency reduction was 2.7 migraine headache days in the melatonin group, 2.2 for amitriptyline and 1.1 for placebo which means that melatonin was as effective as amitriptyline in the primary endpoint of frequency of migraine headaches per month. Melatonin was superior to amitriptyline in the percentage of patients with a greater than 50% reduction in migraine frequency and melatonin was better tolerated than amitriptyline. Melatonin and amitriptyline were both more effective to placebo in reducing the number of analgesics used, and the duration and intensity of migraine headache attacks.


The process of migraines is multifactorial- neurological, vascular, muscular. What we now think is that it can begin when the sensitive nervous system of a migraine sufferer is faced with an environment that can reduce their migraine threshold. These risk and trigger factors include hormonal changes, alcohol consumption, skipping meals, sleep deprivation, medications, and other stressors. Under these circumstances, the neurochemical balance of the nervous system changes, and prodromal symptoms can occur. If this state progresses, the migraine threshold is crossed, and the “migraine generator” area of the brainstem is now activated. A wave like effect occurs across the cerebral cortex- neurons are affected and the trigeminal nerve branches and the vascular structures it supplies are activated. As the branches of the trigeminal nerve are activated, neuropeptides are released from the nerve. These then produce an inflammation of small arteries in the meninges which stimulate platelet aggregation and serotonin release, potentiating the migraine process. Nerve impulses are transmitted back to the brainstem and as the process continues, brainstem reflexes are activated that produce the migraine related symptoms, ex/ nausea, vomiting and photophobia. Pain fiber activation can also result in nasal congestion and pain in the sinus cavities.

While this study did demonstrate efficacy of clinical import, we can do even better. I would definitely incorporate melatonin 3 mg/day into my prophylaxis approach to migraine… in which I am intending to reduce not only frequency, but duration and severity as well.

Reference: Goncalves A, Ferreira A, Ribeiro R, et al. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg andplacebo for migraine prevention. Published online J Neurol Neurosurg Psychiatry May, 2016

157431721I’m regularly looking for more satisfactory results for treatment of acne vulgaris— those nasty pimples most commonly on the facial area. There are multiple factors that cause acne, but a few of those factors includes and excessive production of sebum, an immune response to the bacteria called Propionibacterium acnes, inflammation and abnormal cell turnover of skin cells.

Tea tree leaf oil is one of those plant compounds that has demonstrated both antimicrobial and anti-inflammatory properties. Previous studies have shown effectiveness of tea tree oil in treating acne but they used higher concentrations of the oil (up to 5%) that are currently not available in commercially available products. The purpose of this study was to see if a commonly available tee tree oil gel and facial wash might work for mild to moderate acne.

Both men and women with mild to moderate acne were recruited in Australia. They were ages from 16-39 y.o. Study participants received 200 mg/g of a Tea Tree medicated gel and 7 mg/g Tea Tree Face Wash for Acne. Study subjects used the products twice daily on their face. They applied 1 pump of the face wash, patted it dry, and then applied a small amount of the gel in a thin layer on the acne areas and leave it on for at least 6 hours and then wash it off right before the next application.

The total number of acne lesions were recorded and scored at baseline, 4, 8 and 12 weeks. The amount of skin oiliness was also recorded by the researcher at those same time intervals. Patients also kept a diary and at the end of each week, they recorded their acne on a 5 point scale ranging from worse to significantly better. Tolerance to the tea tree applications were also scored by the investigator. A laboratory testing of the susceptibility of the acne bacteria to the oil and gel and face wash was also done and the minimum inhibitory concentration (MIC) of each product was determined. The MIC of the unformulated oil ranged from 0.25% to 1% which means that 90% of the isolates were inhibited by 1%. The MIC of the gel ranged from 0.062-0.5% and the MIC of the face wash was < 0.25%.

Results: Mean total lesion count significantly decreased at each visit with a 25% decrease at 4 weeks, 37% decrease at 8 weeks and 54% decrease at 12 weeks. The investigator assessment score was significantly better at weeks 8 and 12 compared to baseline. Facial oiliness was significantly improved at week 12 compared to baseline. Clinical efficacy of 40% or greater in lesion count at 12 weeks occurred for 79% (11/14) of the individuals. The weekly opinion of almost half of the men and women with acne was that their acne was about the same or slightly improved by 43%.

No serious adverse events occurred but there was one person who reported minor itching, one with moderate scaling and 1 had moderate peeling and 1 had moderate dryness. The average tolerability scores for erythema and peeling were significantly decreased by the end of the 12 weeks.

Summary and commentary: The use of the gel and face wash containing tea tree oil for 12 weeks did seem to significantly reduce the number of acne lesions and was pretty well tolerated in men and women with mild to moderate acne. Both the gel and face wash showed significant antibacterial activity in the laboratory part of the study which would imply that this mechanism is at least in part, how tea tree works for mild to moderate acne.

Acne is a very common skin condition and I welcome some confirming evidence for tea tree gel and face wash that may help more folks with this pesky problem. It won’t be as simple as that to cure this type of acne. Other influences and strategies that might need to be addressed would include hormonal, diet and stressors.


Malhi HK, Tu J, Riley TV, Kumarasinghe SP, Hammer KA. Tea tree oil gel for mild to moderate acne; a 12 week uncontrolled, open-label phase II pilot study. Australas J Dermatol. March 21, 2016; [epub ahead of print]. doi: 10.1111/ajd.12465.

In the last 3.5 decades, research has proposed a link between several cancers and lower serum levels of vitamin D. Multiple epidemiologic studies have found inverse associations between serum levels of 25-hydroxyvitamin D [25OH)D] concentration and the risk of many cancers including breast cancer, colorectal cancer and prostate cancer. In one randomized controlled trial, women who were given vitamin D and calcium had a 60% reduced incidence in all non-skin cancers compared to those women in the placebo group.[i]

The purpose of the current study was to be more precise in determining any association between 25(OH)D concentration and the risk of non-skin cancer in women 55 years and older. Two different cohorts were used. The first, N=1,169, was one from a randomized controlled clinical trial in Nebraska with a median level of serum vitamin D of 30 ng/mL. The second was from a prospective cohort study of individuals living in 52 countries although 90% were in either the US or Canada, N=1,135, with an average serum D level of 48 ng/ml. By using this approach, the analysis was able to be done across a broad range of 25(OH)D serum levels.

The incidence of all invasive cancers excluding skin cancer was evaluated over several years with a median of 3.9 years was compared in relationship to 25 (OH)D concentrations. The incidence of cancer was lower at higher concentrations of 25(OH)D levels and women with concentrations of 40 ng/ml or more had a 67% lower risk of cancer than women with levels < 20 ng/ml.

506609568Commentary: The results of this analysis support the importance of serum levels and cancer risk and thus direct us more precisely to a target serum level of vitamin D to optimize cancer prevention. The significant risk reduction comes at levels that are considerably higher than the >20 ng/ml considered adequate for bone health, which is the minimum recommended by the Institute of Medicine. I urge patients and practitioners to pay close attention to the units used by their labs. For example, 12-20 ng/ml = 30-50 nmol/L.


Sharon L. McDonnell, Carole Baggerly, Christine B. French, Leo L. Baggerly, Cedric F. Garland, Edward D. Gorham, Joan M. Lappe, Robert P. Heaney. Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study. PLOS ONE, 2016; 11 (4): e0152441 DOI: 10.1371/journal.pone.0152441

[i] Lappe J, Travers-Gustafson D, Davies K, et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007; 85(6):1586-1591.

This randomized double-blind clinical trial was conducted in Iran in women with97623506 cervical intraepithelial neoplasia (CIN) I, as diagnosed with pap smear, colposcopy and biopsy. Women were between the ages of 18 to 55 and had proven CIN 1 based on pap smear cytology and then colposcopy and biopsy. Only those with biopsy proven CIN 1 were included. Women were excluded if they had a history of cervical cancer, other cancers of the lower genital tract, hysterectomy, past treatment of the cervix with cell destructive therapy (ex/ cryotherapy, cautery, conizations), pregnant women or if they were using anti-folate medications.

Women were randomly assigned to receive 5 mg/day of folate (n=29) or placebo (n=29) for 6 months. While the study reports “folate”, it does not clarify if it was in fact folic acid or a form of folate, however, compliance was assessed measuring plasma homocysteine levels. Women were advised not to change their diet or physical activity during the 6 months.

The primary outcome was histology proven CIN 1 and was determined through pap smear cytology, colposcopy and cervical biopsy. Secondary outcomes were glucose homeostasis, lipid profiles, inflammatory factors and biomarkers of oxidative stress.

Four women in the folate group and 5 in the placebo group did not complete the trial, although all 58 women were included in the final analysis. After 6 months of 5 mg/day of folate supplementation or placebo, a greater percentage of women in the folate group had a regression of their CIN 1. (83.3% vs. 52.0%). One patient in the each group progressed to CIN-II. Folate supplementation resulted in a significant decrease in serum insulin, homocysteine, HOMA-B and plasma malondialdehyde, and increased glutathione levels, but it did not affect lipids, reduce fasting glucose, or affect inflammatory or oxidative stress markers.

Commentary: CIN develops in a linear fashion and those with CIN are susceptible to cervical cancer, with greater risks for those who have higher grade lesions (CIN-II, CIN-III), and those with the high risk human papilloma virus (HPV) types, especially HPV 16 and 18. The current study reports that women taking folate (unknown form) at 5 mg/day for 6 months resulted in more women having regression of their CIN 1 to normal, than those in the placebo group. However, it is important to keep in mind that the rates of spontaneous regression of CIN 1, with no treatment, are between 60% and 85% within a 2-year time period. The question in my mind is: Were these results meaningful and due to folate supplementation or within the range of normal regression, whether folate or placebo? Select previous research has found an inverse association between folate levels in the serum and folate in the diet and CIN, while other research did not find a significant relationship. In controlled clinical studies, folic acid supplementation (10 mg/day) has resulted in the improvement or normalization of cytology smears in patients with cervical dysplasia. When patients were treated with folic acid, the regression-to-normal rate, as determined by colposcopy/biopsy examination, was observed to be 20% in one study, 63.7% in another, and 100% in yet another.

Given the totality of the research on folic acid, I will continue to use 5-10 mg/day. As part of my total treatment plan for CIN 1, I typically use 10 mg/day for 6 months, and if cytology/pathology results are then normal, I adjust the treatment plan, including reducing the folate to 5 mg/day for another 6 months. There is a small amount of evidence that women with MTHFR mutations that affect folate metabolism, may have higher risk of cervical cancer. Practitioners could consider testing MTHFR in those women with abnormal pap smears, to determine if supplementation with folic acid or the more expensive folate is an important part of the treatment plan based on MTHFR results.


Asemi Z, Vahedpoor Z, Jamilian M, et al. Effects of long-term folate supplementation on metabolic status and regression of cervical intraepithelial neoplasia: A randomized, double-blind, placebo-controlled trial. Nutrition 2016; 32 (6): 681-6

Menstrual cramps are one of the most common gynecological problems in reproductive aged women. Menstrual cramps due to primary dysmenorrhea (the type of menstrual cramps that are due to a physiological problem, rather than a medical condition such as endometriosis). Primary dysmenorrhea starts after the release of prostaglandins from endometrial cells (those cells that line the inside of the uterus). The target of treatment of acute primary dysmenorrhea has focused on the suppression of the synthesis or function of these prostaglandins. These treatments include non-steroidal anti-inflammatory drugs (NSAIDS), herbal extracts, nutritional supplements and hormonal contraceptives. Most of us are familiar with the role of vitamin D in calcium homeostasis, bone mineralization and immune function. But, vitamin D reduces the expression of cyclooxygenase-2 and thus reduces prostaglandin production, increases prostaglandin inactivation, regulates the expression of prostaglandin receptors, targets the endometrium and thus reduces the intensity of pain as well as possibly has anti-inflammatory effects.

Vitamin DWith the prevalence of primary dysmenorrhea (between 45% and 95%), the prevalence of vitamin D insufficiency, and the influence of vitamin D on prostaglandins, it seems logical that someone would choose to evaluate the effect of vitamin D supplementation on primary dysmenorrhea in women with a vitamin D deficiency.

This randomized double-blind placebo-controlled clinical trial was conducted on 60 Iranian with primary dysmenorrhea and vitamin D deficiency. Women had to have at least four recent consecutive menstrual cycles with painful cramps during the previous 6 months. Women also had to have a serum vitamin D level < 50 ng/ml. (Severe deficiency = < 10 ng/mL; moderate deficiency = 10-19 ng/mL and mild or insufficient = 20-29 ng/mL.) Women in the treatment group (n=30) received 50,000 oral vitamin D once per week for 8 weeks and 30 women received a placebo once weekly for 8 weeks. In the end, 23 women remained in the vitamin D group and 27 women in the placebo group. Among these 50 women, 31 had severe vitamin D deficiency and the remaining 19 had moderate vitamin D deficiency.

After 2 months of treatment, those in the vitamin D group had significant increases in serum levels of vitamin D and none in the placebo group. In the vitamin D treatment group prior to treatment, pain was mild in 3 (13%), moderate in 16 (69.6%) and severe in 4 (17.4%) of the women. After treatment, 22 (95.7%) had mild pain, 1 (4.3%) had moderate pain and none had severe pain. In the placebo group, after the two months of no treatment, 4 (14.8%) had mild pain, 17 (63%) had moderate pain and 6 (22.2%) had severe pain. Pain intensity significantly decreased in the treatment group after 8 weeks of treatment with a significant difference in pain intensity between the two groups after the 8 weeks of treatment and one month after the end of treatment.

Commentary: A weekly dose of 50,000 IU Vitamin D for 8 weeks in women with primary dysmenorrhea and recently determined vitamin D deficiency is a safe, simple, inexpensive strategy to reduce mild, moderate and severe menstrual pains. In a previous 2012 study (Lasco et al.) on vitamin D for primary dysmenorrhea, women received a single dose of 300,000 IU Vitamin D before the beginning of their menstrual cycle and was done in women with low normal vitamin D levels but not deficiency. In the current study, the serum levels of vitamin D increased to sufficient levels (approx. 55 ng/mL). This approach with vitamin D could go a long way to decreasing the need for NSAIDS or even prescription pain pills for women with acute primary dysmenorrhea and a vitamin D deficiency.

Reference: Moini A, Ebrahimi T, Shirzad N, et al. The effect of vitamin D on primary dysmenorrhea with vitamin D deficiency: a randomized double-blind controlled clinical trial. Gynecological Endocrinology 2016, Early Online: 1-4

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