Food GOLD: Turmeric is just as effective as 14 pharma drugs but suffers from NONE of the side effects

Image: Food GOLD: Turmeric is just as effective as 14 pharma drugs but suffers from NONE of the side effects

What if you could replace all the pills in your medicine cabinet with just one herb? Depending on what you take and why, that may be possible with turmeric. Its main component, curcumin, boasts enough health-enhancing properties to keep pharmaceutical execs up at night.

In fact, this herb is so powerful that it has been at the heart of more than 12,000 peer-reviewed biomedical studies. Researchers have found more than 800 different therapeutic and preventive uses for curcumin. Here is a look at just a few of the drugs to which it compares favorably, as outlined by Green Med Info.

Metformin (for diabetes)

Diabetes numbers continue to climb as Americans grapple with obesity, and that means more and more people are taking Metformin – and taking on its scary risks as well. However, a study in the journal Biochemistry and Biophysical Research Community found that curcumin has value in treating diabetes; it is between 500 and 100,000 times more powerful than Metformin when it comes to activating AMPK, which raises glucose uptake. Studies have also shown that it has a 100 percent efficacy rate in preventing those with pre-diabetes from developing full-fledged diabetes.

Lipitor (for cholesterol)

A 2008 study revealed that curcumin compares favorably to atorvastatin, which you may know as Lipitor, when it comes to dealing with the endothelial dysfunction behind atherosclerosis while reducing inflammation and oxidative stress. Other studies have shown that it can impact triglyceride levels, LDL cholesterol, and total cholesterol. While most of the studies so far have been done in animals, it is believed that it could have the same effect in humans, although the right levels have yet to be established.

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Prozac (for depression)

A study in 2011 found that curcumin compares favorably to the antidepressants fluoxetine (Prozac) and imipramine when it comes decreasing depressive behavior. Best of all, it doesn’t carry the serious side effects that Prozac does, which include sleep problems, tremors, headaches, nausea, a lower sex drive, and suicidal ideation. In addition, it’s well-tolerated by patients.

Researchers believe it works on depression by inhibiting monoamine oxidase, the enzyme that has been linked to depression when it’s present in high amounts in the brain. It also raises levels of calmness-inducing serotonin and dopamine.

Oxaliplatin (for chemotherapy)

A study published in the International Journal of Cancer looked at curcumin’s effects in stopping colorectal cell lines from proliferating. The researchers discovered the herb compared favorably to the chemotherapy drug oxaliplatin. Other studies are underway exploring the impact curcumin has on various types of cancer after animal studies showed it could help prevent illnesses like skin, stomach and colon cancer in rats.

Anti-inflammatory medications

Curcumin is also great for inflammation, which is at the root of many chronic illnesses today such as cancer, metabolic syndrome, Alzheimer’s disease, degenerative diseases, and heart disease. A study published in Oncogene identified it as an effective alternative to drugs like ibuprofen, aspirin and naproxen given its strong anti-inflammatory effects, fighting inflammation at the molecular level. Meanwhile, in a study of patients with rheumatoid arthritis, curcumin worked even better than anti-inflammatory drugs.

Curcumin is so effective at addressing such a vast array of conditions that it’s hard to discuss it without sounding like you’re exaggerating. However, turmeric is truly “food gold” and it’s something well worth making a conscious effort to consume more of. You might not be ready to clean out your entire medicine cabinet, but that doesn’t mean you can’t start adding this spice to your food. It pairs well with a variety of dishes, soups, salads, stews, and smoothies; consuming turmeric with fats is ideal, and make sure you add a pinch of pepper to boost its bioavailability.

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Take it from a doctor: Heart surgeon says statins DO NOT work, can even increase risk of diabetes and obesity

Image: Take it from a doctor: Heart surgeon says statins DO NOT work, can even increase risk of diabetes and obesity

If you aren’t taking statins, there is a good chance you know several people who do. After all, a quarter of the American population over the age of 45 takes one daily. Given their widespread use, you would think they are incredibly effective and safe, but nothing could be further from the truth – and some doctors are speaking out about the dangers.

When a respected heart surgeon like Dr. Dwight Lundell, who is the retired Chief of Surgery and Chief of Staff at Arizona’s Banner Heart Hospital, voices his concerns about statins, everyone should take notice. With 25 years of experience and more than 5,000 open heart surgeries under his belt, the doctor recently confessed that he, like many other physicians, has been getting it wrong when it comes to statins.

Dr. Lundell said that statins are no longer working, and the recommendations to take such medications and severely restrict fat intake are “no longer scientifically or morally defensible.”

As you might expect, his comments were not welcomed by the medical industry. Statins are huge money-makers in a population that is rife with obesity, poor eating habits and heart health concerns. Costing anywhere from $53 to $600 per month, drugs like Lipitor have racked up lifetime sales of $125 billion, while Crestor, 2013’s top-selling statin, generated $5.2 billion of revenue that year alone. With more people taking these drugs than ever, why are heart disease-related deaths still rising?

Lundell says that it’s time for a paradigm shift in how heart disease is treated now that we know its true cause is arterial wall inflammation. He said that foods full of sugars and simple carbohydrates, along with processed foods with omega-6 oils, “have slowly been poisoning everyone” and our bodies react to such “foreign invaders” with inflammation in the walls of arteries. If this inflammation is the cause of heart disease rather than high cholesterol, of course, there is no need for cholesterol-lowering statins. The inflammation, he says, causes the cholesterol to accumulate in blood vessel walls, so it’s the inflammation that we need to target.

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Those whose livelihoods depend on statin profits won’t be too thrilled with his advice: “By eliminating inflammatory foods and adding essential nutrients from fresh unprocessed food, you will reverse years of damage in your arteries and throughout your body from consuming the typical American diet.”

They’d much rather have people continuing to bark up the wrong tree, avoiding beneficial fats in favor of the very processed foods that create high cholesterol in the first place so they can convince you that you need their medications to bring it back down – medications that cause a slew of other health problems that will only drive you to need even more pills as the profits pile up.

For example, statins have been shown in studies to double your chances of developing diabetes and raise your risk of suffering serious diabetic complications, and they’ve also been linked to obesity.

Try a natural approach to heart health

So what should you do if you want to enhance your heart health? Increasing your physical activity, regardless of your current level, can make an impact, whether you’re completely sedentary and decide to start taking an evening stroll a few times a week or you already lift weights and choose to increase your reps.

Avoiding the foods Dr. Lundell identified as dangerous for heart health is another step that can make a big difference, so say goodbye to simple sugars and carbohydrates like refined sugar, white bread, and cookies, along with processed food.

While statins aren’t nearly as effective or safe as those who sell them would like you to believe, there are some very simple and affordable ways to keep your heart healthy without any negative side effects.

Are Vegetarian and Vegan Diets Best for Preventing and Treating Diabetes?

I’m going to try to answer a question asked by both patients and care providers: Is a vegetarian or vegan diet the ideal diet for preventing and treating diabetes?

A quick Internet search would yield plenty of popular articles that advocate a vegetarian diet. According to certain websites, such a diet prevents the onset of diabetes or, in the case of confirmed diabetes, enables one to stop treatments.

Of course, such claims are completely false. What’s more challenging, however, is to determine whether a vegetarian diet is the one that should be recommended on a first-line basis in patients with diabetes in the hopes of achieving diabetic control and preventing complications.

Interpret Studies With Caution

Reviews and meta-analyses on this subject conclude rather strongly that diets that are low in or that contain no foods of animal origin are beneficial. We can cite a review that was recently published in Current Diabetes Reports.[1]

It discusses a lower incidence of diabetes in longitudinal studies and decreased glycated hemoglobin levels and diabetes treatments required in randomized studies where a vegetarian diet was compared with low-fat diets. For my part, I think these results and claims—which seem a bit exaggerated to me—need to be seen in relative terms.

In regard to cohort studies, a lot of caution is warranted. Although the incidence of diabetes in certain studies was lower by up to one half in the followers of a vegetarian diet, it must be borne in mind that this is a typical situation where it is impossible to establish a causal link between a way of eating and a disease risk, given the importance of confounding factors. Being a vegetarian is associated, on average, with a largely healthier lifestyle. This is common knowledge.

As for randomized trials, it must be said that they are of short duration. For the most part, when we look at the meta-analyses, we find greater weight loss with vegetarian diets than with the diets tested in the control groups.

The main hypothesis for explaining this difference in weight loss between the groups is that in the open-label studies, the participants in the intervention group were more or less consciously influenced to lose weight, even if, in principle, weight loss was not an objective. Therefore, weight loss would have been what was responsible for the improvement in glycemic control rather than the quality of the diet, per se.

Also, it is well known that high-protein or high-fat diets have a dramatic effect on glycemic control in patients with diabetes, in addition to bringing about rapid weight loss.

What About the Mediterranean Diet?

Last, to the best of my knowledge, no randomized trial has ever compared a vegetarian diet with a Mediterranean-type diet, which contains foods of animal origin. This is a major shortcoming.

Ideally, these diets should be compared if one really wants to conclude that vegetarianism is superior. It is a shortcoming all the more so because there is abundant literature in favor of the Mediterranean diet for preventing and treating cardiometabolic risk factors, and especially for improving glycemic control in diabetics.

Although no clinical trial has compared the vegetarian diet with the Mediterranean diet, there is a recently published network meta-analysis[2] from which one can make an indirect comparison between the vegetarian and Mediterranean diets and, more generally, other types of diets—namely, the Paleo diet, high-protein diet, low-carb diet, and a diet with low glycemic index and load.

The overall finding of this network meta-analysis is in favor of the Mediterranean diet when it comes to glycemic control. The Mediterranean diet seems to be at least as effective or even superior to a vegetarian diet, which does not fare so badly either and which is associated with better diabetes control.

Think Long-term

The answer to the question “Is a vegetarian diet the one to recommend on a first-line basis in patients with diabetes?” is, at least in my opinion, no. My message is that one should recommend a diet that can be followed over the long term.

If the patient chooses a vegetarian diet, one can respect this choice entirely. The same goes for an animal fat–free diet, on the condition that a dietetic follow-up is provided. If, on the other hand, a patient wants to eat a diet containing foods of animal origin, one can very well recommend another balanced and health-friendly diet, the model being the Mediterranean diet.

GWAS Identifies Risk Locus for Erectile Dysfunction and Implicates Hypothalamic Neurobiology and Diabetes in Etiology

Erectile dysfunction (ED) is a common condition affecting more than 20% of men over 60 years, yet little is known about its genetic architecture. We performed a genome-wide association study of ED in 6,175 case subjects among 223,805 European men and identified one locus at 6q16.3 (lead variant rs57989773, OR 1.20 per C-allele; p = 5.71 × 10−14), located between MCHR2 and SIM1. In silico analysis suggests SIM1 to confer ED risk through hypothalamic dysregulation. Mendelian randomization provides evidence that genetic risk of type 2 diabetes mellitus is a cause of ED (OR 1.11 per 1-log unit higher risk of type 2 diabetes). These findings provide insights into the biological underpinnings and the causes of ED and may help prioritize the development of future therapies for this common disorder.

Main Text

Erectile dysfunction (ED) is the inability to develop or maintain a penile erection adequate for sexual intercourse.

ED has an age-dependent prevalence, with 20%–40% of men aged 60–69 years affected.

The genetic architecture of ED remains poorly understood, owing in part to a paucity of well-powered genetic association studies. Discovery of such genetic associations can be valuable for elucidating the etiology of ED and can provide genetic support for potential new therapies.

We conducted a genome-wide association study (GWAS) in the population-based UK Biobank (UKBB) and the Estonian Genome Center of the University of Tartu (EGCUT) cohorts and hospital-recruited Partners HealthCare Biobank (PHB) cohort. Subjects in UKBB were of self-reported white ethnicity, with subjects in EGCUT and PHB of European ancestry, as per principal components analyses (Supplemental Material and Methods).
ED was defined as self-reported or physician-reported ED using ICD10 codes N48.4 and F52.2, or use of oral ED medication (sildenafil/Viagra, tadalafil/Cialis, or vardenafil/Levitra), or a history of surgical intervention for ED (using OPCS-4 codes L97.1 and N32.6) (Supplemental Material and Methods). The prevalence of ED in the cohorts was 1.53% (3,050/199,352) in UKBB, 7.04% (1,182/16,787) in EGCUT, and 25.35% (1,943/7,666) in PHB (Table S1). Demographic characteristics of the subjects in each cohort are shown in Table S2. The reasons for the different prevalence rates in the three cohorts may include a higher median cohort age for men in PHB (65 years, compared to 59 years in UKBB and 42 years in EGCUT; Table S2), “healthy volunteer” selection bias in UKBB,

a lack of primary care data availability in UKBB, and intercultural differences, including “social desirability” bias.

Importantly, we note that the assessment of exposure-outcome relationships remains valid, despite the prevalence likely not being representative of the general population prevalence.

GWASs in UKBB revealed a single genome-wide significant (p < 5 × 10−8) locus at 6q16.3 (lead variant rs57989773, EAFUKBB [C-allele] = 0.24; OR 1.23; p = 3.0 × 10−11). Meta-analysis with estimates from PHB (OR 1.20; p = 9.84 × 10−5) and EGCUT (OR 1.08; p = 0.16) yielded a pooled meta-analysis OR 1.20; p = 5.71 × 10−14 (heterogeneity p value = 0.17; Figures 1A–1C). Meta-analysis of all variants yielded no further genome-wide loci. Meta-analysis of our results with previously suggested ED-associated variants also did not result in any further significant loci (Supplemental Material and Methods; Table S3), nor did X chromosome analysis in UKBB.

Figure thumbnail gr1
Figure 16q16.3 (Lead Variant rs57989773) Is an Erectile Dysfunction-Associated Locus and Exhibits Pleiotropic Phenotypic Effects


The association of rs57989773 was consistent across clinically and therapy defined ED, as well as across different ED drug classes (Figures 1C and S1). No further genome-wide significant loci were identified for ED when limited to clinically or therapy defined case subjects (2,032 and 4,142 case subjects, respectively).
A PheWAS of 105 predefined traits (Table S4) using the lead ED SNP rs57989773 found associations with 12 phenotypes at a p value < 5 × 10−4 (surpassing the Bonferroni-corrected threshold of 0.05/105), including adiposity (nine traits), adult height, and sleep-related traits. Sex-stratified analyses revealed sexual dimorphism for waist-hip ratio (WHR; unadjusted and adjusted for body mass index) and systolic and diastolic blood pressure (Figure 1D; Table S5).
The lead variant at the 6q16.3 locus, rs57989773, lies in the intergenic region between MCHR2 and SIM1, with MCHR2 being the closest gene (distances to transcription start sites of 187 kb for MCHR2 and 284 kb for SIM1). Conditional and joint analysis (Supplemental Material and Methods) revealed no secondary, independent signals in the locus. Previous work has implicated the MCHR2-SIM1 locus in sex-specific associations on age at voice-breaking and menarche.

The puberty timing-associated SNP in the MCHR2-SIM1 region (rs9321659; ∼500 kb from rs57989773) was not in LD with our lead variant (r2 = 0.003, D’ = 0.095) and was not associated with ED (p = 0.32) in our meta-analysis, suggesting that the ED locus represents an independent signal.

To identify the tissue and cell types in which the causal variant(s) for ED may function, we examined chromatin states across 127 cell types

for the lead variant rs57989773 and its proxies (r2 > 0.8, determined using HaploReg v.4.1) (Supplemental Material and Methods). Enhancer marks in several tissues, including embryonic stem cells, mesenchymal stem cells, and endothelial cells, indicated that the ED-associated interval lies within a regulatory locus (Figure 2A; Table S6).

Figure thumbnail gr2
Figure 2Functional Analysis of 6q16.3 Implicates SIM1 in ED Pathogenesis


To predict putative targets and causal transcripts, we assessed domains of long-range three-dimensional chromatin interactions surrounding the ED-associated interval (Figure 2B). Chromosome conformation capture (Hi-C) in human embryonic stem cells

showed that MCHR2 and SIM1 were in the same topologically associated domain (TAD) as the ED-associated variants, with high contact probabilities (referring to the relative number of times that reads in two 40-kb bins were sequenced together) between the ED-associated interval and SIM1 (Figures 2B and S2). This observation was further confirmed in endothelial precursor cells,

where Capture Hi-C revealed strong connections between the MCHR2-SIM1 intergenic region and the SIM1 promoter (Figure 2C), pointing toward SIM1 as a likely causal gene at this locus.

We next used the VISTA enhancer browser

to examine in vivo expression data for non-coding elements within the MCHR2-SIM1 locus. A regulatory human element (hs576), located 30-kb downstream of the ED-associated interval, seems to drive in vivo enhancer activity specifically in the midbrain (mesencephalon) and cranial nerve in mouse embryos (Figure 2D). This long-range enhancer close to ED-associated variants recapitulated aspects of SIM1 expression (Figure 2D), further suggesting that the ED-associated interval belongs to the regulatory landscape of SIM1. Taken together these data suggest that the MCHR2-SIM1 intergenic region harbors a neuronal enhancer and that SIM1 is functionally connected to the ED-associated region.

Single-minded homolog 1 (SIM1) encodes a transcription factor that is highly expressed in hypothalamic neurons.

Rare variants in SIM1 have been linked to a phenotype of severe obesity and autonomic dysfunction,

including lower blood pressure. A summary of the variant-phenotype associations at the 6q16 locus in human and rodent models is shown in Table S7. Post hoc analysis of association of rs57989773 with autonomic traits showed nominal association with syncope, orthostatic hypotension, and urinary incontinence (Figure S3). The effects on blood pressure and adiposity seen in individuals with rare coding variants in SIM1 are recapitulated in individuals harboring the common ED-risk variants at the 6q16.3 locus (Figure 1D), suggesting that SIM1 is the causal gene at the ED-risk locus. SIM1-expressing neurons also play an important role in the central regulation of male sexual behavior as mice that lack the melanocortin receptor 4 (encoded by MC4R) specifically in SIM1-expressing neurons show impaired sexual performance on mounting, intromission, and ejaculation.

Thus, hypothalamic dysregulation of SIM1 could present a potential mechanism for the effect of the MCHR2-SIM1 locus on ED.

An alternative functional mechanism may be explained by proximity of the lead variant (rs57989773) to an arginase 2 processed pseudogene (LOC100129854), a long non-coding RNA (Figure 2A). RPISeq

predicts that the pseudogene transcript would interact with the ARG2 protein, with probabilities of 0.70–0.77. Arginine 2 is involved in nitric oxide production and has a previously established role in erectile dysfunction.

GTEx expression data

demonstrated highest mean expression in adipose tissue, with detectable levels in testis, fibroblasts, and brain. Expression was relatively low in all tissues, however, and there was no evidence that any SNPs associated with the top ED signal were eQTLs for the ARG2 pseudogene or ARG2 itself.

As a complementary approach, we also used the Data-driven Expression Prioritized Integration for Complex Traits and GWAS Analysis of Regulatory or Functional Information Enrichment with LD correction (DEPICT and GARFIELD, respectively; Supplemental Material and Methods)

tools to identify gene-set, tissue-type, and functional enrichments. In DEPICT, the top two prioritized gene-sets were “regulation of cellular component size” and “regulation of protein polymerization,” whereas the top two associated tissue/cell types were “cartilage” and “mesenchymal stem cells.” None of the DEPICT enrichments reached an FDR threshold of 5% (Tables S8–S10). GARFIELD analyses, which assesses enrichment of GWAS signals in regulatory or functional regions in different cell types, also did not yield any statistically significant enrichments, therefore limiting the utility of these approaches in this case.

ED is recognized to be observationally associated with various cardiometabolic traits and lifestyle factors,

including type 2 diabetes mellitus (T2D), hypertension, and smoking. To further evaluate these associations, we first conducted LD score regression

to evaluate the genetic correlation of ED with a range of traits. LD score regression identified ED to share the greatest genetic correlation with T2D, limb fat mass, and whole-body fat mass (FDR-adjusted p values < 0.05; Table S11).

Next we performed Mendelian randomization

(MR) analyses to evaluate the potential causal role of nine pre-defined cardiometabolic traits on ED risk (selected based on previous observational evidence linking such traits to ED risk

), i.e., T2D, insulin resistance, systolic blood pressure, LDL cholesterol, smoking heaviness, alcohol consumption, body mass index, coronary heart disease, and educational attainment (Tables S12–S15). MR identified genetic risk to T2D to be causally implicated in ED: each 1-log higher genetic risk of T2D was found to increase risk of ED with an OR of 1.11 (95% CI 1.05–1.17, p = 3.5 × 10−4, which met our a priori Bonferroni-corrected significance threshold of 0.0056 [0.05/9]), with insulin resistance likely representing a mediating pathway

(OR 1.36 per 1 standard deviation genetically elevated insulin resistance, 95% CI 1.01–1.84, p = 0.042). Sensitivity analyses were conducted to evaluate the robustness of the T2D-ED estimate (Figure S5, Table S13), including weighted median analyses (OR 1.12, 95% CI 1.02–1.23, p = 0.0230), leave-one-out analysis for all variants (which indicated that no single SNP in the instrument unduly influenced the overall value derived from the summary IVW estimate

), and a funnel plot (showing a symmetrical distribution of single-SNP IV estimates around the summary IVW causal estimate). The MR-Egger regression (intercept p = 0.35) provided no evidence to support the presence of directional pleiotropy as a potential source of confounding.

We also identified a potential causal effect of systolic blood pressure (SBP), with higher SBP being linked to higher risk of ED (MR-Egger OR 2.34 per 1 standard deviation higher SBP, 95% CI 1.26–4.36, p = 0.007, with MR-Egger intercept [p = 0.007] suggesting presence of directional pleiotropy). LDL cholesterol (LDL-C) showed minimal evidence of a causal effect (OR 1.07 per 1 standard deviation higher LDL-C, 95% CI 0.98–1.17, p = 0.113), and there was limited evidence to support a role for smoking heaviness or alcohol consumption (Table S15). Genetic risk of coronary heart disease (CHD) showed weak effects on risk of ED, suggesting that pathways leading to CHD may be implicated in ED (OR 1.08, 95% CI 1.00–1.17, p = 0.061). Further, we identified no causal effects of BMI (using a polygenic score or a single SNP in FTO) or education on risk of ED.
Genetic variants may inform drug target validation by serving as a proxy for drug target modulation.

ED is most commonly treated using phosphodiesterase 5 (PDE5) inhibitors such as sildenafil. To identify potential phenotypic effects of PDE5 inhibition (e.g., to predict side effects or opportunities for repurposing), we looked for variants in or around PDE5A, encoding PDE5, which showed association with the ED phenotype. Of all 4,670 variants within a 1 Mb window of PDE5A (chromosome 4:119,915,550–121,050,146 as per GRCh37/hg19), the variant with the strongest association was rs115571325, 26 kb upstream of PDE5A (ORMeta 1.25, nominal p value = 8.46 × 10−4; Bonferroni-corrected threshold [0.05/4,670] = 1.07 × 10−5; Figure S6). Given the weak association with ED, we did not evaluate this variant in further detail.

We have gained insight into ED, a common condition with substantial morbidity, by conducting a large-scale GWAS and performing several follow-up analyses. By aggregating data from 3 cohorts, including 6,175 ED-affected case subjects of European ancestry, we identified a locus associated with ED, with several lines of evidence suggesting SIM1, highly expressed in the hypothalamus, to be the causal gene at this locus. Our findings provide human genetic evidence in support of the key role of the hypothalamus in regulating male sexual function.

Mendelian randomization implicated risk of T2D as a causal risk factor for ED with suggestive evidence for insulin resistance and systolic blood pressure, corroborating well-recognized observational associations with these cardiometabolic traits.

Further research is needed to explore the extent to which drugs used in the treatment of T2D might be repurposed for the treatment of ED. Lack of evidence for a causal effect of BMI on ED risk in MR analysis (using multiple SNPs across the genome) suggests that the association of the lead SNP (rs57989773) with BMI arises from pleiotropy and that the association of this variant with ED risk is independent of its association with adiposity.

In conclusion, in a large-scale GWAS of more than 6,000 ED-affected case subjects, we provide insights into the biological underpinnings of ED and have elucidated causal effects of various risk factors, including pathways involved in the etiology of T2D. Further large-scale GWASs of ED are needed in order to provide additional clarity on its genetic architecture and etiology and to shed light on potential new therapies.

Scientists study Canadian medicinal plants to explore natural cures for diabetes

Image: Scientists study Canadian medicinal plants to explore natural cures for diabetes

Diabetes is a complex disease that leads to a wide variety of complications, one of the most common of which is diabetic nephropathy (DN) or kidney damage. A team of researchers from Canada sought to identify natural extracts, found in the eastern James Bay area, with potent anti-apoptotic properties that can prevent kidney cell death characteristic of DN. Their study was published in BMC Complementary and Alternative Medicine.

When it was first recorded in ancient Egypt, diabetes was considered mainly a rare disease. Today, it has exploded into a worldwide epidemic, with about 422 million sufferers on the planet in 2014. The prevalence of the disease is known to be spreading steadily, particularly in mid- to low-income countries.

One of the most dangerous complications of diabetes is DN, which is usually a precursor to kidney failure when left unaddressed. It is just one of the many results of the abnormal apoptotic process that occurs as a result of diabetes.

Apoptosis or cellular death is a natural process that’s essential to the continued balance of the human body. Because of it, old, dysfunctional cells are replaced by new ones. A proof of its importance is how its absence can cause the development of severe diseases, such as cancer.

But as with everything, too much apoptosis is hardly a good thing. In diabetes, the cells go through apoptosis at an abnormal rate. It usually starts with the death of the pancreatic beta cells, the cells responsible for producing the hormone insulin. The insufficiency in insulin results in a jump in blood glucose levels, which leads to more cellular death. Apart from kidney cells, those in the liver and the nervous system are also at a considerable risk.

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DN is one of the most common offshoots of diabetes among the people of the Cree nation in Canada, according to the study’s authors. This has prompted them to look into potential natural treatments that are readily available in the area. They compiled a list of 17 plant species:

  • Balsam fir – Abies balsamea (L.) Mill.
  • Speckled alder – Alnus incana subsp. rugosa (Du Roi) R.T. Clausen
  • Creeping snowberry – Gaultheria hispidula (L.) Muhl.
  • Ground juniper – Juniperus communis L.
  • Sheep Laurel – Kalmia angustifolia L.
  • Tamarack – Larix laricina Du Roi (K. Koch)
  • Common clubmoss – Lycopodium clavatum L.
  • White spruce – Picea glauca (Moench) Voss
  • Black spruce – Picea mariana (P. Mill.) BSP
  • Jack pine – Pinus banksiana Lamb.
  • Balsam poplar – Populus balsamifera L.
  • Labrador tea – Rhododendron groenlandicum (Oeder) Kron and Judd
  • Northern Labrador tea – Rhododendron tomentosum (Stokes) Harmaja subsp. subarcticum (Harmaja) G. Wallace
  • Tealeaf willow – Salix planifolia Pursh
  • Pitcher plant – Sarracenia purpurea L.
  • Showy mountain ash – Sorbus decora (Sarg.) C.K. Schneid.
  • Mountain cranberry – Vaccinium vitis-idaea L.

Extracts were obtained from specific parts of the different plants. The researchers then took cultures of Madin-Darby Canine Kidney (MDCK) cells, which are cells from a cocker spaniel that are used for biological studies involving the kidneys. They induced damage on the MDCK cells by the administration of a hypertonic medium. This particular step was performed in the presence or absence of each of the 17 plant extracts’ maximal nontoxic concentrations. After 18 hours of treatment, the cells were examined to determine the cytoprotective and anti-apoptotic effects of the extracts. The researchers then looked at the effect of the treatment on the activity of caspases-3, -8, and -9, all of which play an important role in apoptosis.

After the test, the researchers identified Gaultheria hispidula and Abies balsamea as having the most potent cytoprotective and anti-apoptotic effects. The said extracts prevented apoptosis by blocking the activity of caspase-9 in the mitochondrial apoptotic signaling pathway.

Marijuana and Diabetes: What You Need to Know

Medical views and public opinions on cannabis (marijuana) have come a long way in the last several decades. Today, medicinal and recreational use of the plant and its derivatives are quickly gaining both acceptance and popularity.

What does this mean for people with diabetes who may use the plant or its constituents (where it is medically or recreationally legal)?

This article summarizes the major effects of cannabis and the derived compounds on physiology and various health conditions, particularly as they may relate to people with diabetes. However, cannabis and many of the associated products remain illegal at the federal level. Anything written in this article is for informational purposes only and is not intended to serve as medical advice.

Marijuana Laws in the United States

According to The National Organization for the Reform of Marijuana Laws (NORML), thirteen states have decriminalized marijuana use, a whopping thirty-two states have enacted medical marijuana laws, and ten states have fully legalized recreational marijuana use for adults.

Image credit: NORML

Medicinal Uses of Cannabis

It is well-established that there are numerous medicinal properties of cannabis. Reports of medicinal cannabis use date back thousands of years, and more and more studies are being conducted today, with increased tolerance, legal status at the local level, and more widely-accepted view of the potential health benefits.

How does it work? Briefly, our bodies have what is referred to as an endocannabinoid system—that is, the specific cellular receptors that can interact with several different compounds that are found in marijuana and can affect a variety of physiological processes. As can be seen in the diagrams below, these receptors are present in a variety of organs and tissues in humans.


Cannabis contains many different compounds. The two major active compounds are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Researchers note that “available research indicates that the main two compounds, d-9-THC and CBD, whilst having similar effects in certain domains, also have almost opposite effects to one another in other aspects.” This highlights why specific preparations (e.g., CBD only) may be especially useful for treating a particular health condition.

Which health conditions may benefit from the use of cannabis or its derivatives? Since the endocannabinoid system can affect numerous processes, there are many conditions that can be targeted.

Some major conditions that have been proposed for targeting include:

  • Anorexia
  • Autoimmune Diseases (Rheumatoid Arthritis, Multiple Sclerosis, Inflammatory Bowel Disease)
  • Cancers
  • Cardiovascular Disease
  • Glaucoma
  • Liver Disease
  • Nausea
  • Nephropathy
  • Neurodegenerative Diseases (e.g., Parkinson’s, Alzheimer;’s, Huntington’s)
  • Obesity
  • Pain
  • Psychiatric Disorders

So, marijuana can affect a variety of organs and exerts both physical and psychological effects.

Many of these uses are already approved in some or all states where medicinal marijuana is legal. As can be seen, some of these conditions (e.g., nephropathy, cardiovascular disease, obesity) are more prevalent in people with diabetes, which may make medicinal cannabis use more likely in this population. In fact, at least one study reported on the benefits of CBD for the treatment of diabetic cardiomyopathy, while other research has shown that the endocannabinoid system is intimately involved in the development of many diabetes-associated complications, and highlights that several clinical trials have recently explored targeting cannabinoid receptors for treatment.

Marijuana and Blood Glucose Management

The use of cannabis or its preparations can offer treatment for various health conditions, including ones that are more prevalent in the diabetes population. So, can the compounds affect blood glucose control and what should individuals with diabetes take into consideration to stay safe? 

Potential Effects on Blood Glucose Levels

Interestingly, some research has suggested that marijuana users tend to be thinner than non-users and that users may be less likely to develop diabetes. Another study suggested that “chronic cannabis smoking was associated with visceral adiposity and adipose tissue insulin resistance but not with hepatic steatosis, insulin insensitivity, impaired pancreatic β-cell function, or glucose intolerance.”

When it comes to the overall effects of marijuana or its components on blood glucose levels at any specific time of use, no conclusive research is available. Many variables affect blood glucose levels and can include food consumption, medication use, activity, anxiety levels, etc. This means that it’s very important for the individual to self-monitor their blood glucose levels to stay safe.

What to Look Out For

Of course, any person with diabetes should always be on the lookout for hypoglycemia and hyperglycemia and make the appropriate adjustments. Marijuana can affect one’s mental state, so it is important to prepare ahead of time, by setting alarms to check blood glucose levels, or by having another individual with you, who knows about diabetes and can help you check your blood glucose and make the appropriate treatment decisions, if necessary.

Interestingly, a recent study suggested an association between marijuana use and a higher likelihood of developing diabetic ketoacidosis (DKA), a serious and life-threatening complication of diabetes. However, a causal relationship is not clear, the findings are limited by small sample size, and confounding variables, such as income and education level. Patients who used marijuana also happened to have a significantly higher A1c level. It could be that in this case, the cannabis-using population was generally less diligent in their diabetes care for various reasons.


As with using any new medication or recreation drug (such as alcohol), it is imperative that people with diabetes remain in control of their condition by checking their blood glucose levels frequently and adjusting accordingly. If a patient is prescribed medicinal cannabis, it is important to discuss any concerns with a healthcare provider ahead of time and to be extra diligent about checking blood glucose levels frequently during use.

Today, cannabis remains illegal at the federal level, but a gray area is increasingly emerging, for both medicinal and recreational use, as more and more states pass new legislature. We will update this article as more research is conducted, and as state and federal laws are updated.


Akturk HK, Taylor DD, Camsari UM; “Association Between Cannabis Use and Risk for Diabetic Ketoacidosis in Adults With Type 1 Diabetes” (2018) JAMA Internal Medicine doi:10.1001/jamainternmed.2018.5142

Atakan Z; “Cannabis, a complex plant: different compounds and different effects on individuals” (2012) Therapeutic Advances in Pharmacology 2(5): 241-254.

Bancks MP, Pletcher MJ, Kertesz SG, Sidney S, Rana JS, Schreiner PJ; “Marijuana use and risk of prediabetes and diabetes by middle adulthood: the Coronary Artery Risk Development in Young Adults (CARDIA) study” (2015) Diabetologia 58(12): 2736-2744.

Booth M; “Cannabis: A History” (2005) St. Martin’s Press, Picador 1stedition.

Bridgeman MB and Abazia DT; “Medicinal Cannabis: History, Pharmacology, and Implications for the Acute Care Setting” (2017) Pharmacy and Therapeutics 42(3): 180-188.

Horvath B, Mukhopadhyay P, Hasko G, Pacher P; “The Endocannabinoid System and Plant-Derived Cannabinoids in Diabetes and Diabetic Complications” (2012) The American Journal of Pathology 180(2): 432-442.

Leung L; “Cannabis and Its Derivatives: Review of Medical Use” (2011) Journal of the American Board of Family Medicine 24: 452-462.

Muniyappa R, Sable S, Ouwerkerk R, Mari A, Gharib AM, Courville A, Hall G, Chen KY, Volkow ND, Kunos G, Huestis MA, Skarulis MC: “Metabolic Effects of Chronic Cannabis Smoking” (2013) Diabetes Care DC_122303.

National Organization for the Reform of Marijuana Laws (NORML) (2018)

Pacher P and Kunos G; “Modulating the endocannabinoid system in human health and disease—successes and failures” (2013) TheFEBS Journal 280(9): 1918-1943.

Penner EA, Buettner H, Mittleman MA; “The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults” (2013) The American Journal of Medicine 126(7): 583-589.

Rajavashisth TB, Shaheen M, Norris KC, Pan D, Sinha SK, Ortega J, Friedman TC; “Decreased prevalence of diabetes in marijuana users: cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) III” (2012) BMJ Open 2: e000494.

Rajesh M, Muhopadhyay P, Batkai S, et al.; “Cannabidiol Attenuates Cardiac Dysfunction, Oxidative Stress, Fibrosis, and Inflammatory and Cell Death Signaling Pathways in Diabetic Cardiomyopathy” (2010) Journal of the American College of Cardiology 56(25)

Whiting PF, Wolff  RF, Deshpande S; “Cannabinoids for Medical Use: A Systematic Review and Meta-analysis” (2015)JAMA Network 313(24): 2456-2473.

Obscure Asthma Drug Shows Promise for Treating Diabetes

A little-used asthma drug called amlexanox may potentially be repurposed to treat type 2 diabetes, according to findings from a small proof-of-concept study published in the July issue of Cell Metabolism.

Results showed that using the drug for 12 weeks was linked to significantly reduced HbA1c in some patients with obesity, type 2 diabetes, and nonalcoholic fatty-liver disease (NAFLD).

“The overall significant reduction in HbA1c over this relatively short trial indicates that amlexanox can benefit some patients with type 2 diabetes. The reduction in HbA1c is on the order of a [dipeptidyl peptidase-4] DPP-4 inhibitor when given alone over the same time period,” commented first author Elif Oral, MD, director of the MEND Obesity and Metabolic Disorder Program at the University of Michigan, Ann Arbor.

Researchers also looked at baseline inflammation, which revealed an interesting finding: people with higher levels of inflammation responded better.

“Among drug-treated patients, there seemed to be a greater degree of inflammation in responders compared with nonresponders. This is interesting, since we know that inflammatory pathways drive up expression of the targets of amlexanox,” Dr Oral said.

Amlexanox inhibits two enzymes: IKKƐ and TBK1. Studies in mice have shown that inhibiting these enzymes improves weight, insulin resistance, fatty liver, and inflammation.

Another intriguing result: responders showed over 1100 gene changes, and these changes were found only in this group.

“The drug response was characterized by a unique and dramatic molecular signature of gene-expression changes, consistent with what was seen in mouse models, in which expression of energy-expenditure genes were increased. We’re still investigating the importance and significance of these gene-expression changes,” Dr Oral added.

Amlexanox Developed in Japan to Treat Allergies and Asthma

Amlexanox was developed in Japan in the 1980s to treat asthma and allergic rhinitis. However, it requires thrice-daily dosing and was never introduced to the United States, because of heavy competition from more popular medications like montelukast, which can be taken once a day. Even in Japan, the prescription rate was very low, and therefore amlexanox was discontinued this year for commercial reasons.

However, its exact mechanism of action has never been fully investigated. It was not until Dr Oral and colleagues screened 150,000 chemicals, looking for inhibitors of IKKƐ and TBK1, that they hit upon amlexanox as a potential antidiabetes drug.

They first tested amlexanox in mice and did an open-label safety study in humans. Both the animal and human trials pointed to fat tissue as an important target for amlexanox.

So researchers next tested amlexanox in a randomized double-blind placebo controlled study that included 42 obese individuals with type 2 diabetes and NAFLD. Participants were randomized to 12 weeks of 50-mg amlexanox three times daily or placebo.

About one-third of participants showed a robust response to amlexanox, with reductions in HbA1c of ≥ 0.5% percentage points or more, which was significantly different from placebo (= .05). Responders also showed significant decreases in fructosamine, a marker for shorter-term glucose control (= .024).

Similar to results in mice, at 2 to 4 weeks responders showed a transient increase in IL-6, followed by decreased fasting glucose and improved insulin sensitivity. A subgroup of responders with NAFLD showed improvement in fatty liver.

Responders also had higher levels of baseline inflammation than nonresponders or placebo patients, including higher levels of CRP, which correlated with the amount of reduction in HbA1c. And analyses of fat biopsies showed they also had higher baseline activation of genes involved in inflammation.

Fat biopsies also replicated findings from the open-label study in humans, showing responders treated with amlexanox had higher expression of genes involved in energy expenditure and “browning” of fat.

Seven patients in the amlexanox group developed a rash at 4 weeks, which resolved within 2 weeks using local treatment. No other adverse events attributable to amlexanox occurred. This is consistent with the long-term safety profile in Japan, in which about 5% of patients developed rash, Dr Oral pointed out.

“We don’t understand the mechanism for why participants with more underlying inflammation responded better. However, previous work has shown that TBKI and IKKƐ are upregulated in the setting of more inflammation. So it is possible that inflammation oversensitizes the pathway that the drug targets,” she explained.

More Studies Planned

The team is now planning a longer 6-month prospective, randomized study in humans that will test whether individuals with elevated CRP and higher levels of fat inflammation at baseline have better responses to amlexanox.

They also plan another trial in humans that will test amlexanox in combination with mirabegron (Myrbetriq, Astellas Pharma), a pure beta agonist used to treat overactive bladder. The idea is to see whether amlexanox can restore catecholamine sensitivity.

Future studies will also determine the optimal safe dose and dosing regimen for amlexanox.

“If we can really prove that those patients with higher inflammation will respond better with this drug, it will be the first time that such an observation will be made, which is exciting. It’s another way of customizing therapy for patients,” Dr Oral stressed.

The group is currently looking for ways to partner with companies and investors, but currently none are involved.

8 Reasons You’re Waking Up Mid-Sleep, and How to Fix Them

Talk about a rude awakening.
woman laying in bed at night on her cell phone

One minute you’re snoozing peacefully, the next you’re wide awake in the dead of night. Sound familiar? Unless you’re blessed enough to conk out like the most determined of logs, you may have experienced this form of sleeplessness before. Waking up during the night isn’t uncommon—a study of 8,937 people in Sleep Medicine estimates that about a third of American adults wake up in the night at least three times a week, and over 40 percent of that group might have trouble falling asleep again (this is sometimes referred to as sleep maintenance insomnia).

So, what’s causing you to wake up in the middle of the night, and how can you stop it from happening? Here are eight common reasons, plus what you can do to get a good night’s rest.

1. Your room is too hot, cold, noisy, or bright.

Your arousal threshold—meaning how easy it is for something to wake you up—varies depending on what sleep stage you’re in, Rita Aouad, M.D., a sleep medicine physician at The Ohio State University Wexner Medical Center, tells SELF.

When you sleep, your body cycles through different sleep stages: 1, 2, 3, 4, and rapid-eye movement (REM). (Some schools of thought lump together stages 3 and 4.) The first stage of sleep is the lightest, Dr. Aouad explains. That’s when you’re most likely to startle awake because a door slams, a passing car’s headlights shine into your window, or because of some other environmental factor like your room being too hot or cold.

Ideally, your room should be dark, comfortably cool, and quiet when you sleep. This might not all be under your control, but do what you can, like using earplugs and an eye mask to block out errant noise and light, or buying a fan if your room is stifling.

2. You have anxiety.

Anxiety can absolutely wake you up at night,” Nesochi Okeke-Igbokwe, M.D., a physician in New York, tells SELF. In fact, trouble sleeping is one of the most common symptoms of an anxiety disorder, according to the Mayo Clinic. That’s because you can experience anxiety-induced issues that are severe enough to rouse you, like a galloping heartbeat or nightmares.

“Additionally, there are people who may experience what are called nocturnal panic attacks, meaning they may have transient episodes of intense panic that wake them up from their slumber,” Dr. Okeke-Igbokwe says.

If your anxiety regularly wakes you up, Dr. Okeke-Igbokwe recommends mentioning it to your doctor, who should be able to help you get a handle on any underlying anxiety or panic disorder at play. Doing so may involve cognitive behavioral therapy, anti-anxiety medication, or a combination of the two. “Meditation and deep-breathing exercises can also sometimes alleviate symptoms in some people,” Dr. Okeke-Igbokwe says.

3. Your full bladder can’t wait until the morning.

Nocturia—a condition that’s generally viewed as getting up to pee at least once during the night, though some experts say that’s not often enough to qualify—appears to be fairly common. A study in the International Neurourology Journal found that out of the 856 people surveyed, around 23 percent of women and 29 percent of men experienced nocturia.

Causes of nocturia include drinking too much fluid before bedtime, urinary tract infections, and an overactive bladder, per the Cleveland Clinic. Untreated type 1 or type 2 diabetes may also be a factor; having too much sugar in your bloodstream forces your body to extract fluid from your tissues, making you thirsty and possibly prompting you to drink and pee more, according to the Mayo Clinic.

If cutting back on your evening fluid intake doesn’t reduce your number of nightly bathroom trips, consult a doctor for other possible explanations.

4. You had a couple of alcoholic drinks.

Sure, alcohol can make it easy to drift off—even when you’re, say, on a friend’s couch instead of tucked into your bed—but it also has a tendency to cause fitful sleep. This is because alcohol can play around with your sleep stages in various ways. For instance, it seems as though alcohol is associated with more stage 1 sleep than usual in the second half of the night. Remember, stage 1 sleep is the period in which you’re most likely to wake up due to environmental factors. So if you’re looking for quality, sleep-through-the-night rest, it’s worth taking a look at how much alcohol you’re consuming.

Everyone metabolizes alcohol differently depending on factors like genetics, diet, and body size. However, Alexea Gaffney Adams, M.D., a board-certified internist at Stony Brook Medicine, recommends that people stop drinking at least three hours before going to bed to give their bodies time to process the alcohol. Since drinking often happens at night, we realize that can be an optimistic time cushion. Based on your personal factors and how much you drank, you might not need that much. But having some kind of buffer—and drinking plenty of water so you’re more likely to booze in moderation—may prevent alcohol from interfering with your sleep.

Also, Dr. Gaffney Adams notes that drinking alcohol too soon before bed will make you need to pee, increasing the likelihood you’ll wake up in the night to use the bathroom. Double whammy, that one.

5. You’ve got sleep apnea.

If you find yourself jolting awake and feeling like you need to catch your breath, sleep apnea might be the culprit. This disorder slows and/or stops your breathing while you are asleep.

If you have obstructive sleep apnea, the muscles in your throat relax too much, which narrows your airway, causing your oxygen levels to drop, the Mayo Clinic explains. If you have central sleep apnea, your brain doesn’t send the right signals to the muscles controlling your breathing, again causing this potentially harmful drop in oxygen. Complex sleep apnea features characteristics of both conditions.

To diagnose sleep apnea, your doctor may have you do an overnight sleep study that monitors your breathing, according to the Mayo Clinic. The most common treatment for sleep apnea is a continuous positive airway pressure (CPAP) machine, which is basically a mask you wear during sleep to help keep your airways open, but your doctor can help you explore the alternatives if necessary.

6. You have an overactive thyroid gland.

“This gland controls the function of several other organs,” Dr. Gaffney Adams tells SELF. When it’s overactive (also called hyperthyroidism), it creates too much of the hormone thyroxine, which can have ripple effects on many different systems in your body, according to the Mayo Clinic. Common symptoms of an overactive thyroid include trouble sleeping, an increased heart rate, sweating (including at night), anxiety, tremors, and more.

Your primary care physician or an endocrinologist (a doctor specializing in hormones) can test your blood to evaluate your hormone levels. If you do have an overactive thyroid, your doctor can walk you through the potential ways of treating it, including medications to slow your thyroid’s hormone production and beta blockers to reduce symptoms like a wild heartbeat.

7. You ate right before bedtime, or you didn’t eat recently enough before you went to sleep.

“Eating too heavy of a meal too close to bedtime can make it difficult to fall asleep or stay asleep,” Dr. Aouad says. One potential reason behind this is acid reflux, which is when your stomach acid moves up into your throat and causes painful nighttime heartburn. And if you eat food right before bed that makes you gassy, the resulting abdominal pain could drag you out of dreamland, too.

On the flip side, going too long without eating before you sleep can also cause this type of insomnia, Dr. Aouad says. There’s the simple fact that your growling, crampy stomach can wake you up. Hunger could also mess with your blood sugar while you sleep, especially if you have diabetes. Going too long without eating can provoke hypoglycemia, which is when your blood sugar drops too low. This can lead to restless sleep, per the Cleveland Clinic, along with issues like weakness or shaking, dizziness, and confusion. Although hypoglycemia can happen to anyone, it’s much more likely in people with diabetes. If you have the condition, work with your doctor on a plan for keeping your blood sugar stable, including during sleep.

8. You have restless legs syndrome.

Restless legs syndrome, or RLS, may make your lower extremities feel like they are throbbing, itching, aching, pulling, or crawling, among other sensations, according to the National Institute of Neurological Disorders and Stroke (NINDS). If you have RLS, you’ll also feel an uncontrollable urge to move your legs. These symptoms are most common during the evening and night and become more intense during periods of inactivity, like…you guessed it, sleep.

Experts aren’t totally sure what causes RLS, but it seems as though there’s a hereditary factor in the mix, according to the NINDS. Researchers are also investigating how issues with dopamine, a neurotransmitter your muscles need to work correctly, may cause RLS. Sometimes there are other underlying issues bringing about RLS as well, such as iron deficiency.

After diagnosing you with RLS via questions and lab exams, your doctor may prescribe medications to increase your dopamine levels or other drugs, such as muscle relaxants. They may also be able to counsel you on home remedies to soothe your muscles, like warm baths.

To sum it up, there are a bunch of possible reasons you are waking up at night. Some are pretty easy to change on your own, others not so much.

If you think all you need to do to fix this is tweak a habit, like falling asleep with the TV on or chugging a liter of water before bed, start there. If you’ve done everything you can think of and still don’t see a change, it’s worth mentioning your nighttime wakeups to an expert who can help you stay put after you drift off.


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