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Worldwide spread of beneficial blood cell gene variant followed migrations

A new study, "Global Genetic Architecture of an Erythroid Quantitative Trait Locus, HMIP-2," published online July 28, 2014 in the Annals of Human Genetics, tracks the worldwide spread of a beneficial blood cell gene variant as it spread from Africa to everyone around the world. Speaking of genes that followed people out of Africa to everywhere else, two beneficial variants of a gene controlling red blood cell development have spread from Africa into nearly all human populations across the globe, according to a new study led by King's College London. The international team studied the genomes of world populations to look for the origin of changes in a key regulator gene which stimulate fetal hemoglobin production into adulthood. On another note regarding ancient migrations in isolated places today, you also may wish to see another researcher's video on solving the mystery of these people's origin, "First Out of Africa - The totally isolated Tribe of the Andaman (Sky Vision)."

Worldwide spread of beneficial blood cell gene variant followed migrations.
Photo by Gary Gershoff

Fetal hemoglobin is normally found in fetuses and infants, but some patients with inherited blood disorders who are able to keep making it as adults experience milder symptoms of their condition. For example, sickle cell anemia is an inherited blood disorder in which red blood cells behave abnormally and can clog blood vessels, leading to acute unpredictable painful spells called a sickle cell crisis which typically last a week. The recurrent sickle crises and chronic anemia lead to serious complications in the joints, bones, lungs, eyes, brain, liver and kidneys, and early death.

Thalassemia is a group of inherited blood disorders where insufficient hemoglobin - the oxygen-carrier in blood cells - is produced, leading to anemia. Symptoms of beta thalassemia can range from moderate to severe, with the most severe form requiring blood transfusions for the rest of the person's life. The only 'cure' for both sickle cell anemia and beta thalassemia is a bone marrow transplant, but this option is only available to a small number of patients.

Studies have shown that carriers of these conditions are protected against malaria

Having one copy of the sickle cell gene significantly increases your chances of surviving malaria. As a result, these blood disorders are more prevalent in parts of the world where malaria is common. However, sickle cell disease is rapidly emerging as a public health issue both globally and in the UK where it is the most common severe genetic disorder, affecting an estimated 13,000 people.

The new study looked at genetic factors that can reduce the severity of these blood disorders. Typically, our bodies make fetal hemoglobin while in the womb, but then switch to another form of hemoglobin, adult hemoglobin, at birth. However, we continue to produce very small amounts of fetal hemoglobin in adulthood, some more than others. Patients who have the genetic factors that increase fetal hemoglobin production tend to have milder symptoms of their blood disorder.

While studying patients of African and of South Asian descent, the authors noticed that one such factor, a genetic variant controlling the red blood cell regulator gene MYB - 'MYB enhancer variant' - on Chromosome 6, is of similar genetic structure not only in both patient groups, but also in healthy individuals, including those of Northern European origin, where thalassemia and sickle cell disease are rare

This led the authors to suspect that beneficial MYB enhancer variants, which promote fetal hemoglobin in the body, are a general feature of human populations across the world and that they might have a common origin. To test this hypothesis, the team searched for genetic signatures of such variants in public genome data generated from world populations to see whether they existed in other ethnic groups.

They found signatures for two different types of MYB enhancer variants, HMIP-2A and HMIP-B, in major human population groups and in nearly all ethnic groups covered by the data. Both variants occur in Sub-Saharan Africa, but only at low frequencies. In much of the rest of the world the alleles have combined, forming HMIP-2A-B, and this combination is relatively common in Europe, South Asia and China. HMIP-2B separately is common in Far-East Asian peoples and in Amerindians, illustrating their connection across the Bering Strait.

The team also tested recent genome sequence data from our extinct cousins, the Neanderthals and Denisovans, and from the Great Apes, but detected neither HMIP-2A nor HMIP-2B

From this, the authors conclude that MYB enhancer variants that modulate the severity of sickle cell and beta thalassemia have arisen twice in modern humans, in Africa, and then spread to the rest of the world. However, this likely occurred long before inherited blood disorders became prevalent, and thus the environmental factors that favored such variants in these early humans are not clear.

The next stage of the research will explore which selection pressures or benefits might have contributed to the present population distribution of the variants. Selection pressures could include nutritional factors, such as the availability of iron in the diet, or specific demands on red blood cell production, such as adaptation to high altitudes.

Genetic clues help researchers to understand the functions of genes and pathways involved in various diseases

Dr Stephen Menzel, co-author from the Department of Molecular Hematology at King's College London, says, according to the July 29, 2014 news release, Study tracks worldwide spread of beneficial blood cell gene variant, "Patients who have milder versions of blood disorders, thanks to their ability to keep producing fetal hemoglobin, carry genetic clues that are helping us to understand the function of the genes and biological pathways involved in these diseases."

Professor Swee Lay Thein, co-author and Consultant Hematologist at King's College Hospital NHS Foundation Trust, says, according to the news release, "King's Health Partners cares for the largest cohort of sickle cell patients in the UK, with an estimated 2,500 patients. Although a newborn in the UK can now expect to live to adulthood, in adults the disorder has evolved into a chronic debilitating disease with acute or chronic pain and organ complications. We hope our research will help to develop biomarkers and ultimately, preventative treatments for inherited blood disorders."

The study, supported by funding from the Medical Research Council, was a collaboration of clinical and research expertise involving scientists and clinicians from international organizations and King's College London, King's College Hospital NHS Foundation Trust and Guy's and St Thomas' NHS Foundation Trust, part of King's Health Partners Academic Health Sciences Center.

What foods are being researched that can be used as medicine?

In another noteworthy study by different researchers, if you want to find out what foods are being researched that can be used as medicine, you might want to check out various studies in the Journal of Medicinal Food or articles such as "Phytonutrients for bone health during aging" and the Nutrition Journal article, "Apple phytochemicals and their health benefits." There are journals that focus on medicinal foods or phytonutrients and micronutrients. For example, one journal is called Phytomedicine and is published by Elsevier.

There's also the International Journal of Phytomedicine that published studies on pharmacognosy, herbal drugs, natural products, phytomedicine, and phytochemistry. What these journals have in common is that focus on how foods and edible plants can be used in the pursuit of health. The nutrition journals also focus on healing foods and which foods are the most nutrient-dense.

What are some studies this month that focused on medicinal foods? They include the following type of research on super foods and functional foods, including the following fields of research that looks at dietary supplements, phytonutrients, myconutrients (edible mushrooms and fungi), food-based vaccines, vitamins, minerals, peptides, nucleotides, nutrigenomics, lipids, carbohydrates, and safety/toxicology of functional foods and dietary supplements. One noteworthy research article is "A Deficiency of Nutrition Education in Medical Training." Or check out, "Achieving Hunter-gatherer Fitness in the 21st Century: Back to the Future."

You also may wish to check out the abstract of research, "Online Sources of Herbal Product Information." If you look at the various journals that cover the field of nutrition, for example, you may wish to take a look at a new study, "Effect of a Low-Fat or Low-Carbohydrate Weight-Loss Diet on Markers of Cardiovascular Risk Among Premenopausal Women: A Randomized Trial," published online July 16, 2014 in the Journal of Women's Health.

Which is better low-fat or low carbohydrate weight-loss diets?

Both low-fat and low-carbohydrate weight-loss diets can have a beneficial effect on longitudinal measures of blood pressure and blood lipids. In this new study, researchers aimed to assess longitudinal changes in blood pressure and blood lipids in a population of premenopausal women, says the study's abstract. The scientists hypothesized that results may differ by level of adherence to the respective diet protocol and baseline presence of hypertension or hyperlipidemia.

In the study, 41 overweight or obese premenopausal women were randomized to a low-fat or 38 women to a low-carbohydrate diet. As part of the 52-week Lifestyle Eating and Fitness (LEAF) intervention trial, researchers fit linear mixed models to determine whether a change in outcome differed by treatment arm.

The results of the study revealed that within-group trends in blood pressure and blood lipids did not differ (p>0.30). Across study arms, there was a significant decrease in systolic blood pressure (SBP, 3 mm Hg, p=0.01) over time, but diastolic blood pressure (DBP) did not change significantly over the course of the study. Blood lipids (total cholesterol [TC], low-density lipoproteins [LDL], and high-density lipoproteins [HDL]) all exhibited nonlinear trends over time (p<0.01); each decreased initially but returned to levels comparable to baseline by study conclusion (p>0.20). We observed a decline in SBP among women who were hypertensive at baseline (p<0.01), but hypercholesterolemia at baseline did not affect trends in blood lipids (p>0.40).

What the researchers found revealed that their results support that dietary interventions may be efficacious for lowering blood pressure and blood lipids among overweight or obese premenopausal women. However, a decrease in systolic blood pressure (SBP) was the only favorable change that was sustained in this study population. These changes can be maintained over the course of a 1-year intervention, yet changes in blood lipids may be less sustainable. Authors of the study are Foraker, Randi E., Pennell, Michael, Sprangers, Peter, Vitolins Mara Z., De Graffinreid, Cecilia, and Paskett, Electra D.

How healthy is eating a sweet potato?

To find out what the health benefits may be from eating a sweet potato, for example, you might take a look at the study or its abstract, "Sweet Potato (Ipomoea batatas [L.] Lam) - A Valuable Medicinal Food: A Review," published online July 14, 2014 in the Journal of Medicinal Food. If you read the study's abstract, you can see that the sweet potato, also known as Ipomoea batatas (L.) Lam, is an extremely versatile and delicious vegetable that possesses high nutritional value. It is also a valuable medicinal plant having anti-cancer, antidiabetic, and anti-inflammatory activities.

Sweet potato is now considered a valuable source of unique natural products, including some that can be used in the development of medicines against various diseases and in making industrial products. The overall objective of the new review is to give a bird's-eye view of the nutritional value, health benefits, phytochemical composition, and medicinal properties of sweet potato.

The sweet potato as a medicinal food

Specifically, this review outlines the biological activities of some of the sweet potato compounds that have been isolated, the pharmacological action of the sweet potato extract, clinical studies, and plausible medicinal applications of sweet potato (along with a safety evaluation), and demonstrates the potential of sweet potato as a medicinal food. Authors of the study are Mohanraj, Remya and Sivasankar, Subha. Journal of Medicinal Food, July 2014, 17(7): 733-741.

To find out more about the health and nutritional benefits, you also might check out the abstract of a study published online July 16, 2014 ahead of print, in the Journal of Medicinal Food, "Effect of a Low-Fat or Low-Carbohydrate Weight-Loss Diet on Markers of Cardiovascular Risk Among Premenopausal Women: A Randomized Trial."

Which is healthier, the whole diet approach or the low-fat diet?

Another study suggests the whole diet approach to lower CV risk has more evidence than low-fat diets. Researchers say that Mediterranean-style diets are most successful, reports The American Journal of Medicine, Elsevier Health Sciences. A study published online in The American Journal of Medicine back in February 2014 reveals that a whole diet approach, which focuses on increased intake of fruits, vegetables, nuts, and fish, has more evidence for reducing cardiovascular risk than strategies that focus exclusively on reduced dietary fat.

This new study explains that while strictly low-fat diets have the ability to lower cholesterol, they are not as conclusive in reducing cardiac deaths. By analyzing major diet and heart disease studies conducted over the last several decades, investigators found that participants directed to adopt a whole diet approach instead of limiting fat intake had a greater reduction in cardiovascular death and non-fatal myocardial infarction.

Food and health: Whole diet approach versus low-fat diets?

Early investigations of the relationship between food and heart disease linked high levels of serum cholesterol to increased intake of saturated fat, and subsequently, an increased rate of coronary heart disease. This led to the American Heart Association's recommendation to limit fat intake to less than 30% of daily calories, saturated fat to 10%, and cholesterol to less than 300 mg per day.

"Nearly all clinical trials in the 1960s, 70s and 80s compared usual diets to those characterized by low total fat, low saturated fat, low dietary cholesterol, and increased polyunsaturated fats," says study co-author James E. Dalen, MD, MPH, according to the February 5, 2014 news release, "Study suggests whole diet approach to lower CV risk has more evidence than low-fat diets." Dalen is with the Weil Foundation, and the University of Arizona College of Medicine. "These diets did reduce cholesterol levels. However they did not reduce the incidence of myocardial infarction or coronary heart disease deaths."

Carefully analyzing studies and trials from 1957 to the present, investigators found that the whole diet approach, and specifically Mediterranean-style diets, are effective in preventing heart disease, even though they may not lower total serum or LDL cholesterol. The Mediterranean-style diet is low in animal products and saturated fat, and encourages intake of monounsaturated fats found in nuts and olive oil. In particular, the diet emphasizes consumption of vegetables, fruit, legumes, whole grains, and fish.

"The potency of combining individual cardioprotective foods is substantial – and perhaps even stronger than many of the medications and procedures that have been the focus of modern cardiology," explains co-author Stephen Devries, MD, FACC, according to that news release. Devries is with the Gaples Institute for Integrative Cardiology (Deerfield, IL) and Division of Cardiology, Northwestern University (Chicago, IL). "Results from trials emphasizing dietary fat reduction were a disappointment, prompting subsequent studies incorporating a whole diet approach with a more nuanced recommendation for fat intake."

Based on the data from several influential studies, which are reviewed in the article, Dalen and Devries concluded that emphasizing certain food groups, while encouraging people to decrease others, is more cardioprotective and overall better at preventing heart disease than a blanket low-fat diet.

Encouraging the consumption of olive oil over butter and cream, while increasing the amount of vegetables, fruits, whole grains, nuts, and fish promises to be more effective

"The last fifty years of epidemiology and clinical trials have established a clear link between diet, atherosclerosis, and cardiovascular events," concludes Dr. Dalen, according to the news release. "Nutritional interventions have proven that a 'whole diet' approach with equal attention to what is consumed as well as what is excluded is more effective in preventing cardiovascular disease than low fat, low cholesterol diets." Another noteworthy study to peruse is "A ‘Posterior Circulation Stroke’ that Benefits from Vitamins."

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