Diet And Cardiometabolic Deaths

From several years ago is a study the emphasizes what we should all hopefully already know - some foods increase the risk of death from cardiovascular events and other foods decrease that risk.  Here is the Results section from the Abstract; I am bold-fonting the important points for ease of reading:

RESULTS:In 2012, 702 308 cardiometabolic deaths occurred in US adults, including 506 100 from heart disease (371 266 coronary heart disease, 35 019 hypertensive heart disease, and 99 815 other cardiovascular disease), 128 294 from stroke (16 125 ischemic, 32 591 hemorrhagic, and 79 578 other), and 67 914 from type 2 diabetes. Of these, an estimated 318 656 (95% uncertainty interval [UI], 306 064-329 755; 45.4%) cardiometabolic deaths per year were associated with suboptimal intakes-48.6% (95% UI, 46.2%-50.9%) of cardiometabolic deaths in men and 41.8% (95% UI, 39.3%-44.2%) in women; 64.2% (95% UI, 60.6%-67.9%) at younger ages (25-34 years) and 35.7% (95% UI, 33.1%-38.1%) at older ages (≥75 years); 53.1% (95% UI, 51.6%-54.8%) among blacks, 50.0% (95% UI, 48.2%-51.8%) among Hispanics, and 42.8% (95% UI, 40.9%-44.5%) among whites; and 46.8% (95% UI, 44.9%-48.7%) among lower-, 45.7% (95% UI, 44.2%-47.4%) among medium-, and 39.1% (95% UI, 37.2%-41.2%) among higher-educated individuals. The largest numbers of estimated diet-related cardiometabolic deaths were related to high sodium (66 508 deaths in 2012; 9.5% of all cardiometabolic deaths), low nuts/seeds (59 374; 8.5%), high processed meats (57 766; 8.2%), low seafood omega-3 fats (54 626; 7.8%), low vegetables (53 410; 7.6%), low fruits (52 547; 7.5%), and high SSBs (51 694; 7.4%). Between 2002 and 2012, population-adjusted US cardiometabolic deaths per year decreased by 26.5%. The greatest decline was associated with insufficient polyunsaturated fats (-20.8% relative change [95% UI, -18.5% to -22.8%]), nuts/seeds (-18.0% [95% UI, -14.6% to -21.0%]), and excess SSBs (-14.5% [95% UI, -12.0% to -16.9%]). The greatest increase was associated with unprocessed red meats (+14.4% [95% UI, 9.1%-19.5%]).

Talk to your physician about adjusting your diet accordingly. SSBs = sugar-sweetened beverages.

A Gentleman's Agreement

Another article about the gut microbiota and immunity is here.  Abstract:

Our body is colonized by more than a hundred trillion commensals, represented by viruses, bacteria and fungi. This complex interaction has shown that the microbiome system contributes to the host's adaptation to its environment, providing genes and functionality that give flexibility of diet and modulate the immune system in order not to reject these symbionts. In the intestine, specifically, the microbiota helps developing organ structures, participates of the metabolism of nutrients and induces immunity. Certain components of the microbiota have been shown to trigger inflammatory responses, whereas others, anti-inflammatory responses. The diversity and the composition of the microbiota, thus, play a key role in the maintenance of intestinal homeostasis and explain partially the link between intestinal microbiota changes and gut-related disorders in humans. Tight junction proteins are key molecules for determination of the paracellular permeability. In the context of intestinal inflammatory diseases, the intestinal barrier is compromised, and decreased expression and differential distribution of tight junction proteins is observed. It is still unclear what is the nature of the luminal or mucosal factors that affect the tight junction proteins function, but the modulation of the immune cells found in the intestinal lamina propria is hypothesized as having a role in this modulation. In this review, we provide an overview of the current understanding of the interaction of the gut microbiota with the immune system in the development and maintenance of the intestinal barrier.

Immunity and maintenance of the intestinal barrier - crucial to health - are strongly affected by the composition of the gut microbiota, which in turn is strongly affected by diet.  High fiber, active culture yogurt - these are part of a healthy diet and can help maintain a better gut profile.

Maintaining Lean Body Mass While "Cutting"

A regimen for maintaining lean body mass while "cutting" for a drug-free physique competition was studied in a female competitor.  Abstract:

To achieve the criterion appearance prior to competing in a physique competition, athletes undergo preparatory regimens involving high-volume intense resistance and aerobic exercise with hypocaloric energy intake. As the popularity of "drug-free" competition increases, more athletes are facing this challenge without the recuperative advantage provided by performance-enhancing drugs. Consequently, the likelihood of loss of lean body and/or bone mass is increased. The purpose of this investigation was to monitor changes in body composition for a 29-year-old self-proclaimed drug-free female figure competitor during a 32-week preparatory regimen comprising high-volume resistance and aerobic exercise with hypocaloric energy intake. We used dual-energy x-ray absorptiometry (DXA) to evaluate regional fat and bone mineral density. During the initial 22 weeks, the subject reduced energy intake and engaged in resistance (4-5 sessions/week) and aerobic (3 sessions/week) training. During the final 10 weeks, the subject increased exercise frequency to 6 (resistance) and 4 (aerobic) sessions/week while ingesting 1130-1380 kcal/day. During this 10-week period, she consumed a high quantity of protein (~55% of energy intake) and nutritional supplements. During the 32 weeks, body mass and fat mass decreased by 12% and 55%, respectively. Conversely, lean body mass increased by 1.5%, an amount that exceeded the coefficient of variation associated with DXA-derived measurement. Total bone mineral density was unchanged throughout. In summary, in preparation for a figure competition, a self-proclaimed drug-free female achieved the low body-fat percentage required for success in competition without losing lean mass or bone density by following a 32-week preparatory exercise and nutritional regimen.

Thus, consistent with popular conception, a high protein intake was associated with maintenance (actually increase) with decreased body mass and fat mass.  High volume exercise and calorie-cutting were all part of the mix, also consistent with popular practice.

Gene Therapy For Sickle Cell Disease

Here is a paper from several years ago, abstract:

Sickle cell disease results from a homozygous missense mutation in the β-globin gene that causes polymerization of hemoglobin S. Gene therapy for patients with this disorder is complicated by the complex cellular abnormalities and challenges in achieving effective, persistent inhibition of polymerization of hemoglobin S. We describe our first patient treated with lentiviral vector-mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells. Adverse events were consistent with busulfan conditioning. Fifteen months after treatment, the level of therapeutic antisickling β-globin remained high (approximately 50% of β-like-globin chains) without recurrence of sickle crises and with correction of the biologic hallmarks of the disease. (Funded by Bluebird Bio and others; HGB-205 ClinicalTrials.gov number, NCT02151526 .).

So, fifteen months of continued therapeutic benefit was observed.  That's very good and stable for that time period. We'll need to look into, and follow up on, continuing developments in this field; but in general, gene therapy opens up exciting avenues of novel therapeutics to treat a variety of inherited and sporadic disorders.

MicroRNA Biomarkers for Type I Diabetes

Here is a paper from several years ago suggesting that circulating microRNAs (small RNA molecules that affect gene expression) can be used to "predict and diagnose" type I diabetes before clinical symptoms are present.  Abstract:

Type 1 diabetes (T1D) is an autoimmune disease that is clinically silent until the majority of β cells are destroyed. There is an unmet need for reliable and cost-effective biomarkers to predict and diagnose diabetes at an early stage. A number of stable microRNAs (miRNAs) have been reported in serum and plasma and are now being investigated as biomarkers of different diseases. We measured the levels of 745 miRNAs in sera of children with recent-onset T1D and age-matched controls using locked nucleic acid-enhanced (LNA-enhanced) quantitative PCR profiling. Thirty-five miRNAs were significantly different between the groups, and 27 miRNAs were elevated in T1D. Good discriminating power was obtained for 6 miRNAs (miR-454-3p, miR-222-3p, miR-144-5p, miR-345-5p, miR-24-3p, and miR-140-5p), which were not elevated at later stages of diabetes. In silico pathway analysis, based on inferred miRNA target genes, associated glycosaminoglycan biosynthesis as well as PI3K/Akt, MAPK, and Wnt signaling pathways with early stages of T1D. Among the 27 upregulated miRNAs in T1D, 2 miRNAs significantly correlated with hemoglobin A1c (HbA1c), as did 5 of 8 downregulated miRNAs. A total of 134 miRNAs significantly correlated with HbA1c when stratifying hyperglycemia-induced miRNAs from T1D-specific miRNAs. In conclusion, we have identified a serum miRNA pattern of recent-onset T1D and signaling pathways that may be involved in its pathogenesis.

The same principle can apply for early diagnosis of other disorders, and we'll be looking at any progress (if any) made since this article came out.  Note also that study of microRNAs is not only useful for identifying biomarkers but also for identifying the cell signaling that is aberrant in disease (as the end of the abstract suggests), leading the way to possible novel therapies.

Melanesians, Non-Western Diet, And Cardiovascular Disease Risk

Why do some non-Western populations have low rates of stroke and heart disease?  Here is a paper looking at one such population.  Abstract (containing one spelling correction):

OBJECTIVES:

To compare cardiovascular risk factor levels between non-westernized Melanesians, apparently free from stroke and ischaemic heart disease, and healthy Swedish populations, and to analyse, among adult Melanesians, relations with age, sex and smoking status.

DESIGN:

Cross-sectional survey.

SUBJECTS:

(i) Traditional horticulturalists in Kitava, Trobriand Islands, Papua New Guinea, uninfluenced by western diet. this study tested 151 males and 69 females aged 14-87 years with 76% and 80% smokers over 20 years. (ii) Healthy Swedish reference populations.

MAIN OUTCOME MEASURES:

Sitting systolic and diastolic blood pressure, weight, height, body mass index, circumferences of waist, pelvis and mid upper arm, triceps skinfold thickness, fasting serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, estimated low-density lipoprotein cholesterol, apolipoprotein B, apolipoprotein A1 and apolipoprotein (a).

RESULTS:

Compared to Sweden, diastolic blood pressure, body mass index and triceps skinfold thickness were substantially lower in Kitava, where all subjects > or = 40 years were below Swedish medians. Among males > or = 20 and females > or = 60 years systolic blood pressure was lower in Kitavans. Fasting serum total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B were 10-30% lower in Kitavan males > or = 40 and females > or = 60 years. Triglycerides were higher in Kitavans aged 20-39. High-density lipoprotein cholesterol did not differ while apolipoprotein A1 was lower in Kitavans. Apolipoprotein (a) tended to be lower in Kitavans, but the differences were small.

CONCLUSIONS:

Of the analysed variables, leanness and low diastolic blood pressure seem to offer the best explanations for the apparent absence of stroke and ischaemic heart disease in Kitava. The lower serum cholesterol may provide some additional benefit. Differences in dietary habits may explain the findings.

So, dietary differences leading to lean body structure, lower blood pressure, and lower cholesterol levels may explain the better stroke/heart disease profile in Melanesians vs. Swedes.  Of course, genetic differences, not mentioned in this abstract, between the two populations may influence this as well.  What I would like to see is a study comparing people within each population, each group having a different diet.  For example, do Melanesians with a Western diet have higher rates to stroke and heart disease?  What about Swedes on a healthier diet?

What We Eat Is What We Think?

Consider that diet can affect your gut microbiome.  Consider also that gut bacteria produce short chain fatty acids from dietary fiber, so that diet can not only affect what bacterial species are in the gut but what products they produce.  Now, take a look at this article on the “gut-brain axis” mediated in part by lipids, including fatty acids, and this other article on a similar topic.

“We are what we eat,” indeed.  Perhaps, we “think what we eat” as well.

A Cold Of The Soul

In Japan, like the USA, pharmaceutical companies push over-medication.  See this article, abstract:

In Japan, depression provides the most drastic example of the impact of disease awareness campaigns. Until the late 1990 s, the public's attitude toward depression was generally unfavorable, due to the negative connotations of the Japanese word for clinical depression, 'utsubyou'. After the 1999 introduction of the first selective serotonin re-uptake inhibitor, pharmaceutical companies initiated educational campaigns. In order to aid the drug's acceptance, they coined the catchphrase 'kokoro no kaze', which literally means 'a cold of the soul'. Thanks to these marketing practices, antidepressant sales have increased six fold, from ¥ 14.5 billion in 1998 to ¥ 87 billion in 2006. However, the catchphrase 'kokoro no kaze' masked a critical difference between a cold and depression. It falsified the nature of treatment for depression by concealing the putative duration of medication. Owing to this distortion of information, pharmaceutical companies were assured a steady stream of profits. Now, the pharmaceutical industry is shifting its focus from depression to bipolar disorder. Japanese psychiatrists can learn a great deal from their experience with the aggressive marketing of antidepressants. In the case of depression, over-medication arguably did more harm than good. The same risk exists with other conditions, including bipolar disorder.

Sound familiar?  Now, if medication is necessary, take it.  I do.  But take medication that is necessary, as determined by your physician, your own research, and the cooperation between yourself and your health care team. Talk to your physician, and do research.  Medication solely to boost pharmaceutical profits is not the way to go.  Good medications are saviors, antibiotics have saved millions of lives, and we should not reject biomedical advances.  But the Japanese case outlined here describe a case where unnecessary overmedication has taken place.  One must understand the difference.

Mental Stresa And Exercise Recovery

Popular conceptions and anecdotal evidence suggests that chronic mental stress can impair recovery from strenuous exercise, including resistance training. This paper validates that idea with quantitative findings. Abstract:

The primary aim of this study was to determine whether chronic mental stress moderates recovery of muscular function and somatic sensations: perceived energy, fatigue, and soreness, in a 4-day period after a bout of strenuous resistance exercise. Undergraduate resistance training students (n = 31; age, 20.26 ± 1.34 years) completed the Perceived Stress Scale and the Undergraduate Stress Questionnaire, a measure of life event stress. At a later visit, they performed an acute heavy-resistance exercise protocol (10 repetition maximum [RM] leg press test plus 6 sets: 80-100% of 10RM). Maximal isometric force (MIF), perceived energy, fatigue, and soreness were assessed in approximately 24-hour intervals after exercise. Recovery data were analyzed with hierarchical linear modeling growth curve analysis. Life event stress significantly moderated linear (p = 0.027) and squared (p = 0.031) recovery of MIF. This relationship held even when the model was adjusted for fitness, workload, and training experience. Perceived energy (p = 0.038), fatigue (p = 0.040), and soreness (p = 0.027) all were moderated by life stress. Mean perceived stress modulated linear and squared recovery of MIF (p < 0.001) and energy (p = 0.004) but not fatigue or soreness. In all analyses, higher stress was associated with worse recovery. Stress, whether assessed as life event stress or perceived stress, moderated the recovery trajectories of muscular function and somatic sensations in a 96-hour period after strenuous resistance exercise. Therefore, under conditions of inordinate stress, individuals may need to be more mindful about observing an appropriate length of recovery.

Thus, if such stress exists, longer recovery times are required. For optimal gains from exercise regiments, it would therefore be recommended to avoid such stress if possible, which would of course have many other health benefits other than for exercise training.

Another Study On Obesity And Kidney Disease

It should come as no surprise that obesity contributes to chronic kidney disease as explained in this paper.  Abstract:

Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for Chronic Kidney Disease. A high body mass index is one of the strongest risk factors for new-onset Chronic Kidney Disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing Chronic Kidney Disease in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that makes preventive behaviors an affordable option.

Nephrolithiasis is the formation of kidney stones, which are quite painful (I have had them). Chronic kidney disease and kidney cancer are obviously key effectors of morbidity and mortality and anything we can do – including maintaining a healthy body weight – to avoid such outcomes would be well worth it.

High Intensity Exercise And Age

There is the popular misconception that high intensity exercise is for the young, and the aging should just shuffle around a little bit and call it a day.

This paper from several years ago says otherwise.  This doesn't mean an elderly person needs to be doing a "Heavy Duty Mike Mentzer" bodybuilding workout, but there needs to be sufficient stimulus for the exercise to be effective.  Thus, the authors talk about the benefits of "low volume, high-intensity aerobic and/or resistance training" to achieve a variety of health benefits.

Of course, at any age, consult your physician before starting any exercise program, but we see a clear indication that high volume, low intensity does not need to be the way to go for the aging.  High intensity can do a better job.

PTSD And Gene expression: The MicroRNA Connectiom

Here is a fascinating article suggesting that post-traumatic stress disorder is associated with varying levels of certain microRNAs, which can affect gene expression.  Abstract:

Posttraumatic stress disorder (PTSD) affects many returning combat veterans, but underlying biological mechanisms remain unclear. In order to compare circulating micro RNA (miRNA) of combat veterans with and without PTSD, peripheral blood from 24 subjects was collected following deployment, and isolated miRNA was sequenced. PTSD was associated with 8 differentially expressed miRNA. Pathway analysis shows that PTSD is related to the axon guidance and Wnt signaling pathways, which work together to support neuronal development through regulation of growth cones. PTSD is associated with miRNAs that regulate biological functions including neuronal activities, suggesting that they play a role in PTSD symptomatology.

This altered gene expression may be linked to the mechanism of the disorder, both underscoring the seriousness of it and possibly pointing in the direction of therapy.  This article was from several years ago; we will be looking for any updates.