January 22, 2020

New study demonstrates sulforaphane improves glucose control in patients with type 2 diabetes

According to a study published two days ago, researchers demonstrated that sulforaphane improves fasting glucose levels and decreases HbA1c levels in patients with type 2 diabetes.

Insulin resistance is preventable and reversible through lifestyle changes, proper nutrition, supplements, exercise and stress management. Weight loss and exercise are the best treatments for restoring the body’s ability to respond to insulin.

Metabolic syndrome and insulin resistance are a significant health care problem in the United States. Type 2 diabetes affects more than 300 million people. Up to 15% of patients cannot take metformin because of kidney damage risks.

As a result, researchers sought out to identify compounds that may inhibit disease-associated gene expression changes seen with type 2 diabetes.

The researchers constructed a signature for type 2 diabetes based on 50 genes, then used publically available expression datasets to screen 3,852 compounds for drugs that potentially reverse disease. They demonstrated that sulforaphane reduced glucose production by liver cells growing in culture and shifted liver gene expression away from a diseased state in diabetic rats.

Researchers then gave 97 patients with type 2 diabetes patients a concentrated broccoli sprout extracts (BSE) for 12-weeks. As result, BSE reduced fasting glucose in patients with dysregulated type 2 diabetes but not in patients with well-regulated type 2 diabetes. They also observed an association between BMI and BSE-induced change in HbA1c. There were significantly reduced levels of HbA1c after BSE treatment in obese patients with dysregulated type 2 diabetes. BSE was also more effective in lowering fasting blood glucose in patients with elevated triglyceride levels and in patients with high HOMA-IR. The BSE-induced reduction of HbA1c correlated with high fatty liver index.

These results demonstrate that sulforaphane reduces glucose production by NRF2 translocation and decreased expression of key gluconeogenetic enzymes and improves fasting glucose and HbA1c in obese patients with dysregulated type 2 diabetes. Sulforaphane reduces glucose production by mechanisms different than metformin and also protects against diabetic neuropathy, renal failure, and atherosclerosis due to its antioxidative effects.

In addition, there are several nutrients that can play a role in improving insulin signaling such as chromium, zinc, carnosine, benfotiamine, alpha lipoic acid, and inositol.

Also, essential fatty acids should be consumed in our diets for overall health, but most individuals with insulin resistance are deficient. Fish oils improve insulin sensitivity and reduce inflammation. 

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source:  Annika S. Axelsson et al. Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes. Science Translational Medicine, 2017 DOI: 10.1126/scitranslmed.aah4477

New study demonstrates improvements in mental health and oxidative stress with carnitine supplementation in PCOS patients

PCOS is associated with irregular menstrual periods, infertility, obesity, diabetes, excess hair growth, acne, and other hormonal difficulties. The condition occurs when a woman’s body produces slightly higher than normal amounts of testosterone and other sex hormones. This imbalance can cause irregular menstrual periods, weight gain, acne, excess body hair, and/or balding.

Pharmaceutical interventions provide some improvements but they do not correct many of the underlying factors and have side effects that may not be tolerated by patients. Many PCOS patients are overweight and have dietary habits that exacerbate the condition.

Recent research has demonstrated that there is an increased risk of mental health disorders such as anxiety and depression in women with PCOS. Many of us are familiar with carnitine’s role in lipid and carbohydrate metabolism, however, there is evidence of carnitine improving depressive symptoms in those with major depressive disorder. Other studies have also shown reduced oxidative stress with carnitine supplementation.

According to a study published this month in Gynecological Endocrinology, researchers demonstrated that carnitine supplementation improved both mental health parameters and oxidative stress biomarkers in women with PCOS.

In this study. 60 patient with PCOS ages 18-40 were divided in two groups to take either a carnitine supplement (250 mg) or placebo for 12 weeks. These individuals did not change their physical activity or take any additional nutritional supplements.

After 12 weeks of carnitine supplementation, there was a significant reduction in weight and BMI change as well as an improvement in Beck Disability Inventory (BDI) total score and Depression Anxiety and Stress Scale (DASS) scores. In addition, there were changes in plasma total antioxidant capacity demonstrating positive effects on oxidative stress. As a result, there were significant improvements in mental health parameters and biomarkers of oxidative stress compared to the placebo.

Other nutrients to consider to support PCOS:

Studies have shown that an inositol deficiency is common in women with PCOS. There appears to be a reduced ability to process, metabolize, and effectively use inositol from foods which is a distinctive characteristic feature of PCOS. As a result, the nutritional requirements of PCOS patients may not be met by a simple change in the diet and that inositol should be viewed as a conditionally essential nutrient in these women.

Myo-inositol and D-chiro-inositol are both essential for patients with PCOS. The conversion of myo-inositol to D-chiro-inositol is of interest because errors here have been strongly involved in PCOS patients. Strong evidence supports that the body makes D-chiro-inositol from myo-inositol and more evidence suggests that some people are less able to make this conversion than others.  Along this spectrum, people who are completely unable to convert myo-inositol to D-chiro-inositol are only going to benefit from supplementation with D-chiro-inositol. Other people who make the conversion, but with less than optimal efficiency, may benefit from large doses of myo-inositol. And, other individuals in between, might see the best results from a blend of the two. Since this conversion is impaired in individuals with PCOS, it is important to always include D-chiro-inositol with myo-inositol supplementation. D-chiro-inositol is the more potent form of inositol for supporting insulin resistance, however, myo-inositol is need for oocyte quality and maturation. Therefore, supplementing with D-chiro-inositol alone cannot not fulfill myo-inositol’s roles that are specific and different from D-chiro-inositol, since it does not convert to myo-inositol.

Also, essential fatty acids should be consumed in our diets for overall health, but most individuals with insulin resistance are deficient. Fish oils improve insulin sensitivity and reduce inflammation. 

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source:  Jamilian H et al. Oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Gynecological Endocrinology, 2017; 33(6):442-447.

New study demonstrates omega-3 fatty acids increase blood flow to regions of the brain associated with cognition

According to a new study published last Thursday in the Journal of Alzheimer’s Disease, researchers showed through neuroimaging increased blood flow in regions of the brain associated with memory and learning in individuals higher omega-3 levels.

Alzheimer’s disease and related disorders (ADRD) are a group of conditions that cause mild cognitive impairment (MCI) or dementia. These conditions affect one’s ability to function socially, personally, and professionally. It’s important to recognize that Alzheimer’s disease begins long before symptoms start just like many other conditions. There is evidence that simple prevention strategies can reduce the risk of ADRD by as much as 50%.

This study included 166 individuals from a psychiatric clinic in which Omega-3 Index results were available. These patients were categorized into two groups of higher EPA and DHA concentrations (>50th percentile) and lower concentrations (<50th percentile). Quantitative brain single photon emission computed tomography (SPECT) was performed on 128 regions of their brains and each individual completed computerized testing of their neurocognitive status.

Previous research hasdemonstrated that mentally stimulating activities reduce the risk of new-onset mild cognitive impairment even when performed later in life.

SPECT can measure blood perfusion in the brain. In addition, performing various mentally stimulating cognitive tasks will show increased blood flow to specific brain regions. As a result, researchers identified a significant relationships between the omega-3 index and regional perfusion on brain SPECT in areas involved with memory, and neurocognitive testing.

This study demonstrated the positive relationships between omega-3 EPA and DHA status, brain perfusion, and cognition. This is significant because it shows a correlation between lower omega-3 fatty acid levels and reduced brain blood flow to regions important for learning, memory, depression and dementia.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source:  Quantitative Erythrocyte Omega-3 EPA Plus DHA Levels are Related to Higher Regional Cerebral Blood Flow on Brain SPECT, Amen, Daniel G. et al., Journal of Alzheimer’s Disease, doi: 10.3233/JAD-170281, published 18 May 2017



New study demonstrates differences in the gut microbiota and regions of the brain in IBS

According to a new study published on May 1st , UCLA researchers identified a relationship between the gut microorganisms and brain volume in those with irritable bowel syndrome (IBS).

This is the first time researchers have been able to show an association between the gut microbiota and regions of the brain involved in sensory information processing in patients with IBS. These results suggest that signals from the brain can influence the composition of gut microbes and the chemicals in the intestine can shape the human brain’s structure.

Previous animal studies have demonstrated effects of gut microbiome on brain function and behavior as well as the influence of the brain on the composition of microbes in the gut. With that being said, only one human study has confirmed these findings.

Other research has showed evidence for alterations of gut microbiome in people with IBS, but there lacked consistency. In relation to a person’s history with childhood trauma there has been an association with structural and functional brain changes and childhood trauma has also been shown to alter gut microbial composition.

In this study, UCLA researchers collected behavioral and clinical measures, stool samples, and brain images from 29 adults diagnosed with IBS and 23 healthy individuals. They used DNA sequencing to quantify composition, abundance, and diversity of the gut microbiota. The researchers then cross-referenced these gut microbial measures with structural features of the brain.

The samples from those with IBS were clustered into two subgroups based on the composition of the microbes in the gut. One group was similar from the healthy control subjects, while the other differed. Those in the group with an altered gut microbiota had more history of early life trauma and longer duration of IBS symptoms. The two groups also displayed differences in brain structure.

The researchers stated that an analysis of individual’s gut microbiome may become a routine screening test for people with IBS in clinical practice, and in the future, therapies such as certain diets and probiotics may become personalized based on an individual’s gut microbial profile. This is what many of us have done the past several decades in functional medicine.

One may need a combination of botanicals, enzymes, and probiotics to optimize the gastrointestinal environment. Certain diagnostic tests may also be beneficial, including stool testing as well as food antibody testing. In addition, a number of studies have suggested a potential role for serum-derived bovine immunoglobulin/protein isolate (SBI) as a potential therapy for IBS.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Jennifer S. Labus, Emily B. Hollister, Jonathan Jacobs, Kyleigh Kirbach, Numan Oezguen, Arpana Gupta, Jonathan Acosta, Ruth Ann Luna, Kjersti Aagaard, James Versalovic, Tor Savidge, Elaine Hsiao, Kirsten Tillisch, Emeran A. Mayer. Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome. Microbiome, 2017; 5 (1) DOI: 10.1186/s40168-017-0260-z


New study demonstrates magnesium’s role in fracture prevention

According to a new study published in the European Journal of Epidemiology, researchers identified an association between low serum magnesium levels and an increased risk of fracture. Most patients with osteoporosis or osteopenia that want to optimize their bone health are told by their traditional doctor to take calcium and vitamin D, and most never recommend magnesium to their patients. All alternative and integrative practitioners know the essential role of magnesium in several cellular processes including it being a major component in bone (50%).

A magnesium insufficiency is seen in most patients, which can be crucial in addressing and preventing disability in middle-aged to elderly people resulting from fractures.

Bone fractures are one of the leading causes of disability especially among the elderly. It is well-known that calcium, vitamin D, vitamin K and trace minerals play an important role in bone health.

In this study, researchers followed 2,245 middle-aged men over a 20-year period. They found that men with lower serum magnesium levels had an increased risk of fractures, specifically fractures of the hip. The risk of having a fracture was reduced by 44% in men with higher blood levels of magnesium. None of the 22 men who had very high magnesium levels (> 2.3 mg/dl) had a fracture during the follow-up period.

Unfortunately, we do not have a great way to measure magnesium status. For example, serum magnesium which was used in this study only represents only 1% of magnesium stores, so if this is low, they have a severe deficiency. Magnesium is homeostatically controlled in the serum and measuring serum magnesium levels provides many false negatives. By the time your serum is low, you are very deficient as the body cannot maintain the serum magnesium levels. Red blood cell magnesium is definitely better and can be routinely assessed by most labs and it’s surprising to see how many patients are deficient.

As a result, these findings confirm the importance of assessing and addressing magnesium status in all patients but in this case those at an increased risk prevention of fractures.

RBC levels of magnesium do correlate with magnesium intake, however, this may not be the case for the elderly, those with specific GI condition, and those on certain medications. In these individuals increasing the intake of foods rich in magnesium may not increase their blood magnesium levels. It is important to address any underlying issues as well as providing magnesium supplementation.

Most individuals do not experience any symptoms or least associate their symptoms with low magnesium. Since blood magnesium is not routinely tested by traditional doctors and hospitals, it is often missed.

It is also important to consider collagen supplementation was well as to prevent fractures as it does make up a significant component many tissues such as bone.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Setor Kwadzo Kunutsor, Michael Richard Whitehouse, Ashley William Blom, Jari Antero Laukkanen. Low serum magnesium levels are associated with increased risk of fractures: a long-term prospective cohort study. European Journal of Epidemiology, 2017; DOI: 10.1007/s10654-017-0242-2


New study demonstrates bovine colostrum decreases intestinal permeability in athletes

There was an interesting study published 6 days ago in Nutrients on intestinal permeability and athletes. I shared a similar article last July in the American Journal of Clinical Nutrition on heavy exercise induced intestinal permeability in athletes.

When one thinks of nutritional supplements in athletes, they usually think of nutrients that increase enhance energy and sports performance. However, athletes commonly suffer from gut issues that are often not identifies or addressed. ‘Leaky gut’ occurs from dysfunction in the intestinal barrier.  This intestinal barrier in the gut is only one cell layer thick. It is essential for the absorption of nutrients and preventing large molecules and bacteria from getting into the blood stream.

This is a particular problem for those taking part in heavy exercise or any form of vigorous strength training, such as CrossFit athletes, strongman competitors, and powerlifters, which can lead to gut issues in athletes as well as more serious conditions like inflammatory bowel and autoimmune disorders.

Inthis study, researchers demonstrated that oral supplementation with colostrum decreased intestinal permeability which was seen with decreases of zonulin in stool samples.

This double-blind placebo-controlled study including 16 athletes during peak training of competition.  The study compared supplementation for 20 days with 500 mg of bovine colostrum or placebo. Gut permeability was assessed by a lactulose and mannitol absorption test and stool zonulin concentrations. Initial results identified that 6 of the 8 athletes in the colostrum group had increased intestinal permeability. After supplementation, the test results were within the normal range and were significantly lower than at baseline.

This is the first study to demonstrate that supplementation with bovine colostrum decreased and restored intestinal permeability in both urinary lactulose/mannitol ratio as well as fecal zonulin. Previous research demonstrated preventative colostrum supplementation on increased permeability associated with heavy exercise in athletes.

As a result, researchers demonstrated that colostrum supplementation decreased previously elevated intestinal permeability and was able to restore it within 3 weeks of supplementation.

These findings demonstrate the importance of colostrum in preventing leaky gut associated with heavy exercise but also as an important nutrients to consider for athletes. When working with athletes, there is often a disconnect between fitness and health. For those individuals that have a sensitivity to dairy, I would consider serum-derived bovine immunoglobulin/protein isolate (SBI) to normalize the gut microbiota and decrease gut permeability.The other advantage of this for athletes is the addition protein content with BCAAs levels superior to whey and provides high levels of IgG which reduces inflammation decreasing mucosal damage.

As a competitive powerlifter, I work with many of these athletes. Due to the stresses they put on their bodies and increased metabolic demands, many often have debilitating gut issues and inflammatory bowel diseases.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Halasa, M. et al. Oral Supplementation with Bovine Colostrum Decreases Intestinal Permeability and Stool Concentrations of Zonulin in Athletes. Nutrients. 2017 Apr 8;9(4). pii: E370. doi: 10.3390/nu9040370.

New study demonstrates enhanced cognition and cerebrovascular function from resveratrol

Alzheimer’s disease and related disorders (ADRD) are a group of conditions that cause mild cognitive impairment (MCI) or dementia. These conditions affect one’s ability to function socially, personally, and professionally. It’s important to recognize that Alzheimer’s disease begins long before symptoms start just like many other conditions. There is evidence that simple prevention strategies can reduce the risk of ADRD by as much as 50%.

The prevalence of dementia for those over 65 years of age is 14% in men and 32% in women. By the age of 80, sixty three percent of those with dementia are women.

Resveratrol has been widely publicized for its cardiovascular health benefits. However, researchers believe it also has positive effects on the hippocampus, an area of the brain that is critical to functions such as memory, learning and mood.

In a recent study published in Nutrients, researchers demonstrated oral supplementation with resveratrol enhanced both cerebrovascular function and cognition in post-menopausal women, which can potentially reduce the risk of cognitive decline.

Cognitive decline is associated with decreased cerebral blood flow and a reduced ability of cerebral arteries to dilate. There is evidence to suggest that the loss of estrogen may contribute to reduced cerebrovascular responsiveness. As a result, maintaining cerebrovascular function may help optimize mood and prevent cognitive decline.

Resveratrol can act through several mechanisms, including binding and activating estrogen receptors to increase nitric oxide bioavailability and facilitate the vasodilatation for adequate cerebral perfusion.

This study was a 14-week randomized, double-blind, placebo control trial consisting of 72 women. researchers demonstrated that a single 75 mg dose of resveratrol was most efficacious for enhancing global cerebral vasodilatation and cognitive performance.

These results support resveratrol supplementation as a potential strategy for mitigating premature cognitive decline in post-menopausal women. Researchers also observed marginal improvements in mood suggesting possible additional benefits to quality of life in the years following menopause.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Evans, HM et al. Effects of Resveratrol on Cognitive Performance, Mood and Cerebrovascular Function in Post-Menopausal Women; A 14-Week Randomised Placebo-Controlled Intervention Trial. Nutrients. 2017 Jan 3;9(1). pii: E27. doi: 10.3390/nu9010027.

New study investigates potential mechanisms of serum-derived bovine immunoglobulin in patients with IBS

Irritable bowel syndrome (IBS) can be debilitating condition consisting of cramping, abdominal pain, bloating, gas, diarrhea and constipation. IBS can affect and one’s work, sleep and relationships.

A variety of factors have been associated with IBS such as genetic susceptibility, infections, small bowel intestinal overgrowth, deficiencies in tight junction proteins, intestinal abnormalities with bile acid metabolism, changes in GI motility, visceral hypersensitivity, dysregulation of the interaction between the CNS and enteric nervous system, as well as psychosocial factors.

One may need a combination of botanicals, enzymes, and probiotics to optimize the gastrointestinal environment. Certain diagnostic tests may also be beneficial, including stool testing as well as food antibody testing.

Recent studies demonstrated the potential role of low-grade inflammation associated with alterations in the gut microbiome, which can contribute to intestinal barrier dysfunction affecting absorption of water and nutrients as well as an increase antigenic exposure with immune activation leading to further intestinal inflammation and gastrointestinal symptoms.

According to a study published 3 weeks ago in Physiological Reports, researchers evaluated the mechanisms of action and effectiveness of SBI in patients with IBS-D. A number of studies have suggested a potential role for serum-derived bovine immunoglobulin/protein isolate (SBI) as a potential therapy for IBS-D.

This study included fifteen patients with IBS-D base on Rome III criteria that were given SBI twice daily for 8 weeks. Researchers assessed GI symptoms and collected plasma and stool samples to evaluate tryptophan metabolism, intestinal permeability, intestinal microbiota, and expression of genes for tight junction proteins, secretory mechanisms, tissue repair proteins, and chemokines.

As a result, researchers demonstrated that GI symptoms improved over 8 weeks with SBI therapy. These findings are consistent with previous research shown with SBI improving GI symptoms in patients with IBS-D. In addition, the duodenal microbiome showed considerable structure changes with increases in the abundance of Proteobacteria Burkholderiales and Firmicutes Catonella to suggest that the small intestinal microbiome is altered after therapy with SBI and this may play a role in improving epithelial barrier function and modulating immune activation.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Valentin N. et al. Potential mechanisms of effects of serum-derived bovine immunoglobulin/protein isolate therapy in patients with diarrhea-predominant irritable bowel syndrome. Physiological Reports. 017 Mar;5(5). pii: e13170. doi: 10.14814/phy2.13170.

New study demonstrates sulforphane’s influence on genetics and prostate cancer

According to a recent study published in the Journal of Nutritional Biochemistry, researchers identified a pathway that sulforaphane may influence long, non-coding RNAs.

This research provides evidence on how these RNAs may play a critical role in triggering the proliferation of cells to become malignant and metastasize. Previous research has demonstrated that long, non-coding RNAs have an essential role in cellular development and an epigenetic influence by controlling what genes are expressed. Researchers believe that when these are dysregulated, they can contribute to chronic disease and cancer.

In this study, researchers demonstrated that one long, non-coding RNA was decreased four-fold with the treatment of sulforaphane and is upregulated in prostate cancer. As a result, treatment with sulforaphane could normalize these long, non-coding RNA levels which not only may help with cancer prevention but also slow cancer progression.

Prostate cancer is the 2nd most common cancer and the second leading cause of cancer-related deaths in the United States in men.
Earlier studies have demonstrated that cruciferous vegetables with a high concentration of sulforaphane help reduce the effects of environmental carcinogens. Sulforaphane targets several biological pathways that modulate Phase I enzymes and elevate Phase II enzymes that are present in all cells.

Once inside the cells, sulforaphane sends a signal to individual cellular enzymes that turns on the natural cellular defenses in these cells. Sulforaphane is capable of restoring the gene’s activity towards normal cell progression. Cells are naturally equipped with their own internal defense system. Much of the cell’s ability to defend itself is due to two main factors: sulforaphane’s ability to produce the antioxidants that quench harmful free radicals and detoxification enzymes to break down toxins.

This study reinforces the importance of diet and nutrition and their epigenetic influence on telling the DNA how to function by turning on and off genes. Other nutrients such as essential fatty acids, curcumin, EGCg, and vitamin D play an important role as well.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Laura M. Beaver, Rachael Kuintzle, Alex Buchanan, Michelle W. Wiley, Sarah T. Glasser, Carmen P. Wong, Gavin S. Johnson, Jeff H. Chang, Christiane V. Löhr, David E. Williams, Roderick H. Dashwood, David A. Hendrix, Emily Ho. Long noncoding RNAs and sulforaphane: a target for chemoprevention and suppression of prostate cancer. The Journal of Nutritional Biochemistry, 2017; 42: 72 DOI: 10.1016/j.jnutbio.2017.01.001

New study demonstrates b vitamins may reduce the negative effects from air pollution

According to a new study published in PNAS, researchers at Columbia University demonstrated that B vitamins may play an essential role in reducing the impact of air pollution. This is the first study to show possible interventions that prevent or minimize the adverse effects of air pollution.

This study shows how preventive measures with B vitamins can influence specific pathways that may mitigate the adverse effects of air pollution.

The World Health Organization (WHO) estimates that approximately 92% of the population lives in places where air quality levels exceed the limits of 10 μg/m3. Air pollutants can deposit in the respiratory tract which can result in lung and systemic inflammation. Although there has been substantial lowering of air pollution through large-scale emissions control policies over the past few decades, adverse health effects are still common.

The negative health effects of air pollution and its role in one’s health may contribute to many complex issues.
In this study, researchers gave participants a placebo or B-vitamin supplement containing folate, pyroxidine, and cobalamin. Plasma B vitamin levels were assessed before and after which demonstrated that B-vitamin supplementation prevented changes in the genes involved in mitochondrial oxidative energy from air pollution.

The truth is, we all live in an ever-increasing toxic environment. More than 80,000 chemicals are introduced into the world each year and our indoor environment is likely more toxic than our outdoor environment.

We are exposed to pesticides, herbicides, chemical solvents, xenobiotics, and industrial chemicals of all kinds that we get exposed through the food we eat, the water we drink and the air we breathe. These toxins accumulate in our body and contribute to the total toxic load that can cause a variety of health problems. Unfortunately, this exposure to chemicals are unavoidable in the environment,
What can we do? Support our detoxification pathways. There is significant evidence on the importance of diet and nutritional supplementation in maintaining detoxification pathways. This may consist of eating organic food, drinking clean, pure water, and supplementing with nutrients like B-vitmains, N-acetyl-cysteine and calcium d-glucurate or participating in a formal detoxification program.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: B vitamins attenuate the epigenetic effects of ambient fine particles in a pilot human intervention trial, Jia Zhong et al., PNAS, doi: 10.1073/pnas.1618545114, published online 13 March 2017