In fluke experiment, espresso quells rare genetic disease

PARIS: A lot of people say they cannot live without coffee, but for one 11-year-old boy living in France, that may be literally true.

June 11, 2019

When his parents accidentally bought decaffeinated capsules recently, a rare genetic muscular disorder -- which they knew could be held in check by two shots of espresso per day -- flared up, provoking uncontrollable and painful muscle spasms.

Four days of agony, anguish and doctor´s visits followed before his parents realised their mistake.

Once they boy started drinking the caffeinated brew again, the symptoms subsided.

"It´s one of those amazing cases of serendipity that dot the history of medicine," said Emmanuel Flamand-Roze, a doctor at Pitie-Salpetriere Hospital in Paris and lead author of a study published Tuesday about the disease afflicting his patient.

Unwittingly, Flamand-Roze told AFP, the parents had carried out what scientists called a double-blind placebo experiment -- the most rigorous test possible to see if a drug or treatment actually works.

The "double blind" part means that neither the patient nor the persons carrying out the experiment know whether the medicine is the real thing of a inert fake.

In this case, the accidental test proved the efficacy of caffeine as a treatment of dyskinesia -- a family of disorders characterised by violent, involuntary muscle movements -- caused by a mutation in the ADCY5 gene.

One in a million 

"The arms, legs and face all move wildly," Flamand-Roze explained.

"This child couldn´t ride a bike, walk home from school, write with a pencil -- a seizure-like crisis could strike at any time."

ADCY5-related dyskinesia is a roughly one-in-a-million disease, and there is no known cure.

The gene in its normal state provides instructions for making an enzyme that helps to regulate muscle contraction.

The mutation disrupts that process, and caffeine helps to restore it.

Doctors had long known that strong coffee helps quell the muscle spasms, but the condition is so rare that there are not enough patients to conduct an experiment in which one group take the "medicine", and another imbibes a look-alike -- in this case, a taste-alike -- placebo.

Such an experiment would, in any case, probably raise ethical issues, since researchers would know ahead of time that the placebo group would likely suffer severe discomfort.

The condition is also known as facial myokymia, and is sometimes misdiagnosed as cerebral palsy.

The symptoms typically appear as sudden jerks, twitches and tremors, and writhing, and usually begin between infancy and late adolescence. The movements can occur during waking hours or at night.

The problem can also strike internally with the respiratory muscles.

The study was published in the US-based Annals of Internal Medicine.

https://www.thenews.com.pk/latest/482689-in-fluke-experiment-espresso-quells-rare-genetic-disease

CRISPR Gene Editing Fixes Muscular Dystrophy in Dogs. Are Humans Next?

The powerful gene editing technology CRISPR is one small step closer to treating a human disease.

By ALICE PARK 

August 30, 2018

In a new paper published in Science, researchers led by Eric Olson, professor and chair of molecular biology at UT Southwestern Medical Center, reported that he and his team successfully used CRISPR to correct the genetic defect responsible for Duchenne muscular dystrophy in four beagles bred with the disease-causing gene. It’s the first use of CRISPR to treat muscular dystrophy in a large animal. (Previous studies had tested the technology on rodents.) In varying degrees, the genetic therapy halted the muscle degradation associated with the disease.

Duchenne is caused by mutations in the dystrophin gene, which codes for a protein essential for normal muscle function. People born with the disease are often eventually confined to wheelchairs as their muscles continue to weaken, and in the later stages, many rely on ventilators to breathe as their diaphragm muscles stop working. Eventually, they develop heart and respiratory failure.

Olson and his team “fixed” the mutated dystrophin gene in four dogs by splicing out an offending section of the gene using CRISPR. The gene editing technology, discovered in 2012, can cut out sections of DNA at precise locations (and also potentially introduce new DNA as well). In the case of Duchenne, says Olson, simply snipping out a section of the mutated dystrophin gene allows the gene to make enough of the proper protein that muscles need to function.

Olson tried two different methods of injecting the CRISPR molecular scissors. With two dogs he directly injected the CRISPR technology into muscle, while in two other dogs he injected the same CRISPR technology into the bloodstream, so it could travel to more parts of the body and have a broader effect on different types of muscle from the limbs to the heart and diaphragm. Because Duchenne seems to affect the heart and respiratory system muscle preferentially, he also loaded the CRISPR cutting complex onto a molecular vehicle, a cold virus that was modified to seek out and splice DNA in those muscle cells in particular.

“I was frankly exuberant by the results,” says Olson. “It was jaw dropping.”

In the dogs that had received the systemic injections, he found that muscle cells in various parts of their bodies, including the heart and diaphragm, were churning out healthy dystrophin protein at anywhere from 3% to 90% of the normal levels eight weeks after injection. Olson says that muscular dystrophy experts believe that if dystrophin levels in affected people were raised to 15% of normal, it would make a dramatic difference in their lives and their ability to function. The dogs receiving the CRISPR injections directly into their muscle also showed higher levels of dystrophin production, but just in those muscles specifically. Because Duchenne affects deep organs like the heart and respiratory system, Olson says finding a way to deliver CRISPR more widely, without repeated and multiple injections, is preferable.

The idea is that CRISPR would essentially delete the mutation in muscle cells, and return the affected dogs to a nearly normal state. So far, the animals continue to make higher amounts of dystrophin after eight weeks.

The study is the latest in an encouraging string of results in applying CRISPR to treat human disease. Researchers have also successfully used the gene editing technology to splice out HIV from both infected human cells in the laband in living mice and rats, and are close to beginning trials to blood disorders like beta thalassemia and sickle cell anemia. Scientists have even corrected a genetic heart defect in embryos in the lab, which were not allowed to develop further or be implanted for ethical reasons. While serious questions about the safety of CRISPR-based therapies remain — some studies revealed greater than expected side effects from overzealous DNA snipping, for example — both academic and commercial researchers remain committed to investigating CRISPR as a new tool in addressing genetic diseases such as Duchenne.

Olson is encouraged by the results, even if they came from just a few dogs. They provide some reassurance that Duchenne, which is often diagnosed before people start to notice symptoms of muscle weakness, might be halted in its tracks before important skeletal, heart and breathing muscle are damaged beyond saving. A CRISPR-based therapy, he says, may be most effective in treating young people recently diagnosed with the disease, to prevent them from ever experiencing the symptoms of Duchenne.

Even people with more advanced disease might benefit, Olson thinks, as long as there is some muscle left to maintain a certain level of function, whether that’s moving the legs and arms or keeping the heart functioning. “I absolutely believe that whatever stage we intervene with this therapy, it could halt or slow the progression of the disease from that point forward,” he says.

First, however, more studies need to be done in larger animals like dogs. Olson is planning on a longer term study to see how long the CRISPR cells remain in the dogs, and how safe the therapy is.

The hope is that if those animal studies and human trials prove this technique is safe and effective, CRISPR could potentially lead to a cure for Duchenne, Olson says. “We are going for a cure, not a treatment,” he says. “All of the other therapies so far for Duchenne muscular dystrophy have treated the symptoms and consequences of the disease. This is going right at the root cause of the genetic mutation.”

http://time.com/5382101/crispr-muscular-dystrophy-in-dogs/

Eating protein at all three meals could help seniors stave off muscle decline

New research from Canada suggests that over-60s should eat protein at all three daily meals to help stave off age-related muscle decline, which can contribute to loss of independence and  falls.

Eating protein at all three meals could help seniors stave off muscle decline

AFP Relax News•August 4, 2017

Researchers at McGill University in Canada studied the effects of protein consumption on muscle strength in seniors.

Older adults tend to get most of their protein from just one of their daily meals -- dinner -- whereas to help preserve their physical strength, protein consumption should be spread out throughout the day, the researchers conclude.

For the study, published in the American Journal of Clinical Nutrition, the scientists tracked more than 1,700 healthy adults aged between 67 and 84 for three years. Participants underwent yearly hand, arm and leg strength testing, as well as mobility tests.

Over the three years, the researchers found that overall physical performance worsened in both men and women, with muscle strength fading more significantly than mobility.

However, participants who consumed protein more evenly throughout the day appeared to retain greater muscle strength -- although not greater mobility -- than those who consumed most of their protein late in the day.

Current recommendations to ensure sufficient protein intake are 1.2g of protein per kilogram of weight for adults of all ages. For example, a man weighing 75kg should eat 90g of protein per day.

For older individuals, this may need to be increased by between 50% and 90%, depending on individuals' lifestyles.

In general, one portion of protein is equivalent to 30g of meat, chicken or fish, one egg, one tablespoon of peanut butter, one-quarter cup of cooked beans or one-half ounce of nuts or seeds, according to the US Department of Agriculture, which recommends that over-50s eat five to seven portions of protein per day, or 150g to 200g.

The study is available here: http://ajcn.nutrition.org/content/106/1/12.extract

https://www.yahoo.com/beauty/eating-protein-three-meals-could-help-seniors-stave-131701757.html

18 Foods That Promote Muscle Growth and Definition

Rich in high-quality protein and omega 3-fats, this food helps combat the chronic inflammation that plagues most people in poor health. Plus: 17 other wonder foods that make your muscles toned and lean, including the one which contains a week's worth of vitamins in just one cup.

2 September 2016

Story at-a-glance

• A number of foods can be helpful when trying to improve muscle growth and definition. Incorporating these foods into your meals on a regular basis may help you get lean and toned
• Eighteen helpful foods are noted, including ones high in healthy fats and high quality protein, such as wild salmon, raw nuts, grass-fed beef, whey protein, coconut oil, olive oil, MCT oil and avocados
• Beneficial fruits and vegetables include spinach, kale, broccoli, sprouts, berries, bananas, watermelon, grapefruit, papaya and mushroom

By Dr. Mercola

If you're looking for muscle growth and definition, there's no getting around exercise. However, you cannot exercise your way out of a poor diet, and when it comes to muscle definition, one of the keys is to lose body fat, or else you will not be able to see the muscles in the first place.

The common belief is that if you want to build muscle, you need to eat lots of protein and carbohydrates because carbs fuel your muscles and protein builds them up. However, the evidence that has emerged over the past several years shows us it's not that simple.

One particularly intriguing finding is that your body has a mechanism that allows it to build muscle even when deprived of food. As it turns out, amino acids and protein serve not just as building blocks for tissues and muscle.

Certain amino acids — most notably branched chain amino acids like leucine — also signal muscle genes to grow and to build protein, and they do that even during times of food deprivation as long as these amino acids are circulating through your blood stream.

Moreover, research reveals that high-carbohydrate diets are a disaster for most people, as they promote insulin and leptin resistance, which actually in turn promotes muscle wasting.

Similarly, eating more protein than your body actually needs — which is usually far less than most people are eating, whether they're athletes or not — may promote elevated blood sugar, weight gain and kidney stress, and may even stimulate cancer growth. I'll discuss suggested dosage recommendations further below.

Foods That Promote Muscle Definition

Nutritionist, fitness trainer and author of "The Sugar Impact Diet," JJ Virgin, recently published an article listing seven foods that can help you get lean and toned.1

Chef and three-time bodybuilding champ, Carlo Filippone, founder and CEO of Elite Lifestyle Cuisine, has also compiled a list of 20 foods that help build and tone muscle.2

Known as "The Muscle Chef," Filippone recommends including these foods in your cooking as often as possible. Below I will summarize a number of their suggestions, along with some of my own.

1.Wild-Caught Alaskan Salmon

Rich in high-quality protein and the anti-inflammatory omega-3 fats docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), wild salmon helps combat the chronic inflammation that plagues most people in poor health. Animal-based omega-3 fats also helps build muscle.3 As noted by Filippone:

"These [fats] go a long way in inhibiting muscle breakdown and supporting strong blood circulation."

Besides healthy fat and protein, salmon also contains leucine. Granted, with 100 grams of salmon providing you with about 1.6 grams of leucine, there's no way you could get the recommended 8 grams of leucine from salmon, but it does contain higher amounts than most other foods.

Wild Alaskan salmon also tends to be low in mercury, which is a serious concern when you're trying to improve your health. Canned wild Alaskan salmon is a less expensive option than salmon steaks.

2.Avocado

Avocados are high in potassium, important for water balance regulation and recuperation after physical exertion, and healthy monounsaturated fat that your body can easily burn for energy.

As with olive oil, the fat in avocados can help with weight management. One study found that eating just one-half of a fresh avocado with lunch helped boost satiation and curb snacking.

The fat in avocados also helps your body absorb fat-soluble vitamins and minerals from other foods (and/or supplements).

Research4 has shown that consuming a whole fresh avocado with tomato sauce or raw carrots significantly enhanced absorption of the carotenoids and conversion of them into an active form of vitamin A.5

Avocados also provide nearly 20 essential nutrients, including vitamins B, E and folic acid.

The greatest concentration of beneficial carotenoids is in the dark green flesh of the avocado, closest to the peel, so you're best off peeling your avocado with your hands, like a banana.

3.Spinach

Spinach is high in niacin, zinc, protein, fiber, vitamins A, B6, C, E and K, thiamin, folate, calcium, iron, magnesium, phosphorus, potassium, copper and manganese. In other words, it's loaded with nutrition for every part of your body.

Abundant flavonoids in spinach also help keep cholesterol from oxidizing and protect your body from free radical damage. The folate in spinach helps promote a healthy cardiovascular system, and magnesium helps lower high blood pressure.

Moreover, research suggests there may have been something to Popeye's ability to turbo-charge his muscles with spinach after all, as the dietary nitrate found in spinach actually helps increase production of proteins that boost muscle strength.6

Studies also have shown that spinach helps maintain your brain function, memory and mental clarity. To retain the rich iron content of spinach, lightly cook it and add a splash of lemon juice or vinegar on top.

4.Coconut Oil

Coconut oil provides a mix of medium-chain triglycerides (MCTs), including caproic acid (C6), caprylic acid (C8), capric acid (C10) and lauric acid (C12). MCTs are an ideal fuel for your body.

However, since nearly 50 percent of coconut oil is lauric acid, which has a longer carbon chain, coconut oil is not necessarily an ideal source of MCTs.

MCT oil is a better alternative if you're looking for ketone production specifically, although you could opt for FRACTIONATED coconut oil, which contains primarily C8 and C10, the former of which readily converts to ketones.7

That said, coconut oil has many tremendous health benefits. For example, your body converts lauric acid into monolaurin, a monoglyceride that can destroy viruses and gram-negative bacteria. This is undoubtedly part of what makes it so medicinally useful.

5.MCT Oil

I recently wrote an extensive article on MCT oil that you can read for further information. Remember that your body processes MCTs differently from the long-chain fats in your diet. Normally, a fat taken into your body must be mixed with bile released from your gallbladder and acted on by pancreatic enzymes to break it down in your digestive system. MCTs don't need bile or pancreatic enzymes.

Once they reach your intestine, they diffuse through your intestinal membrane into your bloodstream and are transported directly to your liver, which naturally converts the oil into ketones. Your liver then releases the ketones back into your bloodstream, where they are transported throughout your body. They can even pass the blood-brain barrier to supply your brain with energy. MCTs also have a thermogenic effect, which has a positive effect on your metabolism.8

For these reasons, MCTs are readily used by your body for energy rather than being stored as fat. Most commercial brands of MCT oil contain a combination of C8 and C10 fats. My personal preference is straight C8 (caprylic acid), as it converts to ketones far more rapidly than do C10 fats. 

6.Kale

Kale has many things going for it, including very high amounts of protein and lots of highly bioavailable calcium. One cup of raw kale contains 2 grams of protein, 7 grams of carbs and 1 gram of fiber (for a net carb value of 6 grams). Like meat, kale contains all nine essential amino acids needed to form the proteins your body needs, plus nine other non-essential ones for a total of 18.

The vitamins offered by just 1 cup of kale can also trump a whole week's worth of other foods: 684 percent of the daily value of vitamin K, 206 percent of the suggested daily amount of vitamin A and 134 percent of vitamin C.

7.Broccoli

Sulforaphane, a naturally occurring organic sulfur compound found in broccoli is probably most well-known for its anti-cancer activity. However, as Filippone points out, sulforaphane also "increases testosterone levels and staves off the retention of body fat."

It also "blocks certain enzymes that have been linked to joint destruction, so broccoli is a must have in an active person's diet." Research has also shown sulforaphane helps protect your muscles against exercise-induced damage.9

8.Sprouts

Sprouts are a concentrated source of nutrition, allowing you to get more nutrients with less bulk. If you're looking for high-quality protein, look no further than sprouts. These little powerhouses are also up to 30 times more nutrient-dense than homegrown organic vegetables.

Sprouting also makes most of the nutrients more bioavailable. Some of the most common sprouts include alfalfa, mung bean, wheatgrass, peas, broccoli and lentils. My personal favorites are sunflower and watercress.

9.Berries

Berries contain concentrated amounts of the disease-fighting phytochemicals that boost your immunity and protect your heart. For a sweet treat, berries are a good choice as they're high in fiber and lower in sugar than many fruits, making them less likely to destabilize your insulin levels.

In particular, blueberries have several known health benefits. They exert positive effects upon your lipid profile, reducing your risk for type 2 diabetes. And because of their bountiful antioxidants, blueberries are one of the best fruits to protect you from premature aging.

10.Bananas

Being high in glucose and digestible sugars, bananas are best avoided if you struggle with insulin resistance or excessive weight. Barring that, bananas are a popular pre- or post-workout food, thanks to their potassium content. Potassium is a mineral that tends to be exhausted by intense exercise, so potassium-rich foods are highly recommended. One banana contains 467 milligrams (mg) of potassium, which is also important for controlling your heart rate and blood pressure.

11.Watermelon

According to Filippone: "Eating watermelon has been shown to improve lipid profiles and lowers fat accumulation, because of its concentration of anthocyanin, a compound that mollifies fat-storage genes. It's refreshing, aides in hydration and can also help reduce muscle soreness after a strenuous workout. I usually melon ball them into a small container and use them as a pick-me up between reps."

That said, be careful when eating any melon, including watermelon, as they do not digest well with other foods. Melon frequently causes digestive problems unless consumed by itself, so ideally, do not eat any other food 30 minutes before or after eating watermelon.

12.Grapefruit

Filippone recommends eating a grapefruit before your workout to aid rehydration (which in turn also aids weight loss), as grapefruit is 90 percent water. Pink grapefruit is also a good source of vitamins A and C (providing 53 percent and 120 percent of the recommended daily value respectively) as well as fiber and potassium.

Red grapefruit contains a bit more flavonoids and anthocyanins than white or pink grapefruit. It also contains lycopene, which helps lower triglycerides, help fight free radical damage and protect your skin from UV damage from the sun.

I recommend consuming grapefruit in moderation due to its fructose content, which may be harmful to your health in excessive amounts. Also beware that grapefruit may, in rare cases, interfere with certain medications, so if you're on meds, be sure to discuss it with your doctor.

13.Papaya

Papaya and other vitamin C-rich foods may help lower your cortisol level after intense exercise. In one study, men who consumed 1,000 mg of vitamin C per day for two weeks had significantly lower cortisol following a 2.5-hour run compared to the placebo group.10

Unripened papaya has yet another advantage. In its unripened state, papaya contains higher amounts of digestive-resistant starch, which is important for optimal gut health. The same goes for unripened bananas and mangos. Resistant starches, which are indigestible, also do not result in blood sugar spikes.

While both ripe and green (unripe) papaya are rich in antioxidants, fiber and papain (an enzyme that helps with protein digestion and dampens inflammation), green papaya contain higher amounts of papain and potassium.

14.Raw Nuts

Magnesium is important for muscle growth and strength, and raw nuts are an excellent source. Nuts such as macadamias and pecans are also excellent choices because they're high in healthy fats while being lower in net carbs. Macadamia nuts have the highest fat and lowest protein and carb content of any nut, and they also happen to be one of my favorites.

Raw macadamia nuts also contain high amounts of vitamin B1, magnesium and manganese. Just one serving of macadamia nuts provide 58 percent of what you need in manganese and 23 percent of the recommended daily value of thiamin. Moreover, about 60 percent of the fatty acid in macadamia is the monounsaturated fat oleic acid. This is about the level found in olives, which are well known for their health benefits.

Pecans are a close second to macadamia nuts on the fat and protein scale, and they also contain anti-inflammatory magnesium, heart healthy oleic acid, phenolic antioxidants and immune-boosting manganese.

15.Grass-Fed Beef

As noted by Virgin: "Beef that's been raised conscientiously is a perfect source of protein, healthy fats and nutrients. Grass-fed beef also comes loaded with the multi-tasking amino acid L-glutamine to help build muscle while preventing muscle breakdown."

Grass-fed beef is also an excellent source of conjugated linoleic acid (CLA), which has potent anti-inflammatory activity. Just be mindful of the amount of protein you eat (all protein, not just that from beef). Most Americans consume three to five times more protein than they need. For most people, a more ideal protein intake is likely around one-half gram of protein per pound of lean body mass, which for most amounts to 40 to 70 grams per day.

If you eat more protein than your body requires, most of those calories will simply be converted to sugar and then fat. Excessive protein can also have a stimulating effect on an important biochemical pathway called the mammalian target of rapamycin (mTOR), which plays an important role in many cancers.

When you reduce protein to just what your body needs and no more, mTOR remains inhibited, which helps minimize your chances of cancer growth. Additionally, when you consume too much protein, your body must remove more nitrogen waste products from your blood, which stresses your kidneys. Chronic dehydration can result, as was found in a study involving endurance athletes.11

16.Mushrooms

Mushrooms are a natural source of vitamin D, which is critically important for muscle function. Muscle weakness is a classic symptom associated with vitamin D deficiency. Besides that, many mushrooms also have other medicinal qualities, including improved immune function.

It's important to eat organically grown mushrooms because they absorb and concentrate whatever they grow in — good or bad. Mushrooms are known to concentrate heavy metals, as well as air and water pollutants, so healthy growing conditions is a critical factor.

17.Olive Oil

While many recommend cooking with olive oil, this is not recommended as high temperatures will cause the olive oil to oxidize and go rancid. Coconut oil, raw grass-fed butter or even lard are better options for cooking. That said, olive oil, used COLD, drizzled on salads, is a healthy fat with many health benefits. As noted by Filippone:

"Olive oil contains … monounsaturated fat, which has been shown to raise serotonin, a hormone associated with satiety, in your blood levels. You'll feel fuller after a meal prepared with olive oil, which will help keep you from indulging in extra calories at mealtime."

However, be aware that olive oil is a common target of food fraud. Even "extra virgin" olive oil is often diluted with other less expensive oils, such as hazelnut, soybean, corn, sunflower, palm, sesame, grape seed or walnut. These other oils will not be listed on the label, nor will most people be able to discern that their olive oil is not pure.

If you live in an area where olive oil is made, buying from a local producer is the ideal solution as it allows you to know exactly what's in your oil. If not, try an independent olive oil shop that can tell you about the growers, or do your research and seek out a brand name you trust.

18.Whey Protein

Whey protein is the perfect "fitness food" as it contains not only high-quality protein, but also extremely high amounts of leucine. Leucine serves multiple functions in your body, one of which is signaling the mTOR mechanism to increase protein synthesis and build muscle. The highest concentrations of leucine are found in dairy products; particularly quality cheese and whey protein.

The typical requirement for leucine to maintain body protein is 1 to 3 grams daily. However, to optimize its anabolic pathway, you need an estimated 8 to 16 grams of leucine per day. While you'd have to eat an enormous amount of leucine-containing foods to reach this amount, you only need 3 ounces of high-quality whey to reach 8 grams of leucine. This makes whey an obvious choice.

Ideally you'll want to consume the whey about 30 minutes before your workout to help increase both fat burning and muscle building. The whey meal will stop the catabolic process in your muscle and promote protein synthesis towards recovery and growth.

On strength training days you could add a serving after your workout. Keep in mind there's only a two-hour window after exercise during which your body will fully use the proteins you ingest for optimizing muscle repair and growth, so your timing is important.

One of the reasons whey works so well is that it is a protein that assimilates very quickly, and will get to your muscles within 10 to 15 minutes of swallowing it. This makes it easier to supply your muscles with the right food at the right time.

A study12 published in the journal Medicine and Science in Sports & Exercise showed the amino acids found in high-quality whey protein activate certain cellular mechanisms, including mTOR, which in turn promote muscle protein synthesis, boost thyroid function and protect against declining testosterone levels after exercise. You just need to be careful that you are not chronically stimulating mTOR on a daily basis, as most studies suggest it will decrease your lifespan.

http://fitness.mercola.com/sites/fitness/archive/2016/09/02/18-foods-for-muscle-growth.aspx?