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The Failure of Alzheimer’s Drugs

https://www.drperlmutter.com/the-failure-of-alzheimers-drugs/

By anyone’s definition, we must now consider Alzheimer’s disease to be an epidemic. Alzheimer’s is a progressive degenerative neurological condition that actually has its origins decades before the initial symptoms of cognitive decline begin to appear. Unfortunately, by the time these symptoms of the disease emerge—memory loss, cognitive decline, and behavioral shifts—there is very little that can be done as, according to our most well-respected medical journals, there is currently no meaningful pharmaceutical treatment for this condition. Despite this reality, pharmaceutical companies continue to market “Alzheimer’s drugs” to the tune of some $3-4 billion annually.
Pharmaceutical Treatments for Alzheimer’s are Failing Us

To be clear, a meaningful pharmaceutical intervention for this devastating condition would absolutely be welcomed by patients and healthcare providers alike. However, as of today, the available Alzheimer’s drugs do not address the underlying disease process, they only attempt to address some symptoms. And, in some cases, these drugs may even worsen cognitive decline.

Despite the optimistic news headlines, Alzheimer’s drugs continue to fail in actual clinical trials. Millions upon millions of the dollars that are spent every year trying to unlock the mysteries of this condition continue to come up empty when it comes to finding a meaningful treatment. In fact, Pfizer, one of the world’s largest pharmaceutical companies with an R&D arm that spends billions of dollars a year developing drugs for profitable markets, has announced that they are no longer trying to find a cure for the disease.

Maybe it’s time to shift our focus.
What’s the Science?

Last year, JAMA Network Open published the findings of a meta-analysis that sought to evaluate the results of 10 high-quality, peer-reviewed studies conducted on two common classes of Alzheimer’s drugs: cholinesterase inhibitors (ChEls) and memantine. These studies represent the experiences of more than 2,500 patients suffering from Alzheimer’s and the results were telling. Not only did the drugs fail to meaningfully treat the symptoms of Alzheimer’s, they were associated with a significantly increased rate of cognitive decline. It’s worth saying this again: cholinesterase inhibitors, which are the largest and most frequently prescribed class of drugs used in the “treatment” of Alzheimer’s disease, have been associated with the worsening of symptoms of the disease they are intended to treat.

Memantine was also shown to be ineffective in a recent study published in the Journal of the American Medical Association. Researchers sought to examine the impact of vitamin E (alpha-tocopherol) and memantine—both alone and together—on the progression of Alzheimer’s Disease. This double-blind, placebo-controlled, randomized clinical trial—the gold standard of clinical research—found that once again memantine was associated with more cognitive decline in Alzheimer’s patients when compared to a placebo. Interestingly enough, vitamin E alone had a positive impact on cognition, but this effect was neutralized when it was paired with memantine.
The Cornerstone of Alzheimer’s

Clearly, we have very little to show for the mountain of time, effort, and financial resources that have been spent searching for a meaningful intervention for Alzheimer’s. While there should be continued interest in developing drug-based therapies, the focus should really be on prevention. Based on some of our most well respected, peer-reviewed research we do know that there are many steps that are clearly associated with reduced risk for this disease. These lifestyle-based interventions, including exercise, diet, sleep, and stress management, all function to address the cornerstone of Alzheimer’s disease: inflammation.

At its core, Alzheimer’s is a bioenergetic breakdown. It represents the failure of the brain to power itself using the fuel to which it is most accustomed: glucose. Many people think that Alzheimer’s results in the destruction of brain cells, but patients suffering from Alzheimer’s have an abundance of functional neurons—they just aren’t functioning. As Alzheimer’s advances, the affected neurons lose their ability to utilize glucose for fuel and therefore lay idle and unused. This shutdown is ultimately precipitated by high blood sugar, which causes insulin resistance; the more insulin resistant our bodies become, the less our brain cells are able to metabolize glucose. However, exciting new research has demonstrated that ketones, a fuel source our bodies produce from fat, have the ability to “repower” these idle neurons and put them back to work in the brain.

This view of the pathogenesis of Alzheimer’s is backed up by the reproducible correlations we consistently see between blood sugar and dementia. One recent study published in the New England Journal of Medicine found that even mild elevations in blood sugar could be tied to an increased risk of developing dementia. What is even more frightening is that this relationship holds true even in individuals who are not diabetic.
Alzheimer’s Prevention

Viewing Alzheimer’s as an inflammation-driven bioenergetic failure allows us to formulate lifestyle-based approaches to the prevention and treatment of the disease. Furthermore, a focus on controlling inflammation has a trickle-down effect: because inflammation underpins virtually every chronic condition we face today, approaching the prevention of Alzheimer’s disease in this way may well help lower your risk for diabetes, heart disease, and cancer.

The most important step for lowering the risk of developing Alzheimer’s disease is to control blood sugar, ideally keeping the fasting blood sugar below 90. As such, it is worthwhile to consider buying an at-home glucose monitor to follow blood sugar levels closely. And the best dietary approach to lower blood sugar to the ideal range is to dramatically reduce the consumption of sugar and refined carbohydrates while welcoming healthful fats back to the table. One of the ways to accomplish both of these goals is to adhere to a ketogenic diet.

In addition to controlling blood sugar, it’s also critically important to exercise regularly, get quality sleep, and manage stress.

Additionally, an increasingly popular area of interest as it relates to inflammation is the role of the microbiome, or resident bacteria, primarily those that reside in the gut. The microbiome plays a critical role in controlling metabolism and, by extension, inflammation. So taking steps to support gut health is another essential step towards preventing Alzheimer’s. Supplementing your diet with probiotics and prebiotic fiber, while avoiding artificial sweeteners, refined carbs, toxic pesticides, and heavy metals are helpful ways to nurture the microbiome and allow it to function properly.
The Path Forward

Unfortunately, we live in a time in which Alzheimer’s has no cure. Nonetheless, it is, to an important degree, a preventable situation. The research is clear, and we have clinicians across the country who are recognizing the fundamental importance of focusing on Alzheimer’s prevention. Considering the demographics of our aging population and the sky-high costs of managing this condition ($250 billion in 2018), it becomes painfully clear that this is a public health crisis.

Unfortunately, powerful market forces are standing in the way of these advances. Unlike pharmaceuticals, no one can patent, license or otherwise monetize broad interventions like diet and exercise. Even though these steps are well-established for the important roles they play in paving the way for brain preservation, our current paradigm does not encourage the prevention narrative of Alzheimer’s—only its treatment.

It is the responsibility of healthcare providers as well as families and loved ones of Alzheimer’s patients to increase awareness of this narrative and champion the cause of prevention.

—
Alzheimer’s – The Science of Prevention

alzheimers_docuseries_prevention

In this groundbreaking documentary series, David Perlmutter, MD, board-certified neurologist and #1 NYT bestselling author, along with leading experts in the field of brain health, reveal the powerful ways you can decrease your chances of developing Alzheimer’s disease.

Register now to be the first to know when each episode is available to watch FREE for 24 hours.

Haven't seen many Spars this year, especially not the local one, in fact I think I saw more Hobbies. They seem to have dropped from #1 spot a few years back and are now outnumbered by the Kestrels and Buzzards.

Earlier I went for a rather disappointing walk over some different fields. There are lots of gnarly old oak trees, some of which are usually inhabited by Little Owls, but I saw and heard none, or the Barn Owls even though I stayed out until dusk. They were our commonest owl, Barn Owls second, Tawnies third but come to think I haven't seen or heard many of any of them since the Beast From The East. Short Eared Owls are coming in along the coast, mostly in winter but in the past I've seen them in most months. Long Eared Owls are occasionally reported but as masters of concealment not by me.

No Lapwings let alone Golden Plovers, not even any Fieldfares or Redwings, or even Linnets. A small flock of about 8 Yellowhammers and about the same number of Bullfinches, and some tits mostly Long Tailed and Blue and a couple of Goldcrests. I saw a magnificent male Kestrel, later being chased by a Rook, and heard a distant Buzzard, and that was petty much it except for the regulation Rooks, Jackdaws, Gulls, Pheasants and Partridges.

I walked round the lake that the farmer dug on top of the hill, but since he died there was naff all there either, it used to have a huge roost of Greylags in winter and Barnacles and various ducks and waders all year. Also he had a couple of Black Swans.

Oh well, it was a nice walk as the sun went down, definitely a three sausage day (with PSB).

Those Great Spotted Woodpeckers can be a pain, some years ago one hammered out the weld in my nut feeder and all the peanuts fell on the ground.Come to think, I haven't seen or heard as many of them as usual, though there are still some Green Woodpeckers to be found.

Quite likely, steroids are #1 culprit but many other drugs may also be causal.

On the other side of that coin, much work shows low carb and especially keto diets to be beneficial against an increasing number of "mental" diseases, not just epilepsy, and some recent work suggests chronic inflammation may be a factor in depression.

A Jim Johnson paper

Mild Suppression of Hyperinsulinemia to
Treat Obesity and Insulin Resistance

http://sci-hub.hk/10.1016/j.tem.2018.03.018

on a similar subject

Ten-year weight gain is associated with elevated fasting insulin levels and
precedes glucose elevation

http://sci-hub.hk/10.1002/dmrr.2986

some excellent folks on Twitter come up with these studies and some of them are even dieticians

The lame food advice at my diagnosis, why it didn’t work, and my #1 Bright Spot solution

I’ll never forget the diabetes food advice I received from my doctor at diagnosis:

“You can eat whatever you want, as long as you take insulin for it.”

In my view, this advice is misleading, overly simplistic, and damaging. In fact, I’d nominate it for the “worst” diabetes food advice out there. Unfortunately, those who are newly diagnosed tell me it is still common. Ugh.

Eating “whatever I wanted” and taking insulin for it was the worst kind of blank check – it set me up for years of out-of-control high blood sugars, deep and prolonged lows, huge guesstimated insulin doses (and therefore big mistakes), mood and energy swings, and lots of diabetes frustration. My blood sugar rarely stayed in my target range (70-140 mg/dl), since the effort required was so high.

It wasn’t until I took some nutrition classes in college, shared a dorm with a bodybuilder, started writing at diaTribe, and began using a continuous glucose monitor (CGM) that I landed on the food advice below: eating fewer carbs and more fat had a game-changing impact on my diabetes, insulin dosing burden, overall health (including cholesterol), and quality of life. In Bright Spots & Landmines, this advice appears first in the book for a reason – it’s been the most important tool for improving my life with diabetes. I’ll follow up next month with an updated list of foods I currently eat, recipes, and interesting new food tricks I’ve been testing.

More here: https://diatribe.org/best-and-worst-diabetes-food-advice

http://drhyman.com/blog/2016/12/21/4-big-fat-food-lies-make-fat-sick/

Since the release of my book Eat Fat, Get Thin, I’ve noticed fierce debates on social media and other news sources about things like calorie counting, eating vs. avoiding fat and genetics.

When it comes to overall health and weight loss, there’s an excess of advice out there. Unfortunately, most of it is terrible, misguided, outdated and scientifically disproven.

This ubiquitously poor advice can create weight loss roadblocks and even damage your health. Here are four prevalent misguided myths that drive me nuts.

Myth #1 – All Calories are Created Equal

A calorie is a calorie, right? Wrong. This myth that refuses to die keeps people from getting and staying healthy, as well as losing weight and keeping it off.

The current thinking is as long as we burn more calories than we consume, we will lose weight. The multi-billion dollar weight loss industry perpetuates this lie and actually relies on you believing it to stay afloat.

Thinking that losing weight is all about energy balance or calories in/calories out, vastly oversimplifies the truth. The food industry and government agencies love this myth because it keeps you buying more junk food, which they suggest you eat in moderation. How’s that working out for America?

Truth is, there are good and bad calories. Your body is much more complex than a simple math problem. When we eat, our food interacts with our biology, a complex adaptive system that instantly transforms every bite. Food is more than just calories and flavors. Food is information telling our cells what to do.

In fact, every bite you eat affects your hormones, brain chemistry and metabolism. Sugar calories cause fat storage and spike hunger. Calories from fat and protein promote fat burning. What counts more is the quality, not the quantity, of the calories.

The highest-quality calories comes from whole foods. Calories from high-quality whole foods are naturally lower in calories as compared with processed foods. This is why calorie counting isn’t necessary when you eat fresh foods like those your great-grandma made.

These foods include quality proteins such as grass-fed animal products (not factory-farmed), organic eggs, chicken, small wild fish, nuts and seeds. It means good fats like avocado, extra-virgin olive oil, coconut butter and omega-3 fats from fish. And it includes good carbs like vibrantly colored vegetables (the brighter the better), fruits like wild berries, apples and kiwis, and super foods like chia and hemp seeds.

Myth #2 – Your Genetics Define You and Your Health

Most conventional doctors still believe we are predispositioned to weight gain due to familial history. In other words, if your mom is fat and your grandma is fat, that’s why you became fat. You drew the fat card or the diabetes card in the genetic lottery.

As a firm believer that food is medicine and information for our cells, I can assure you our genetics do not dictate future health outcomes. We possess much more power over them.

Consider this: There are 32 obesity-associated genes in the general population that account for only 9 percent of obesity cases. Even if you had all 32 obesity genes, you would put on only about 22 pounds.

Our genes only change 2 percent every 20,000 years. About 35 percent of Americans are obese today, yet by 2050 that number will rise to over 50 percent. Our genes simply don’t evolve that fast to keep up with the increase.

What changed drastically wasn’t our genes. It was that we went from eating about 10 pounds of sugar, per person, per year in 1800 to 152 pounds of sugar (and 146 pounds of flour) per person, per year today. These pharmacological doses of sugar and flour hijack our metabolism and make us fat and sick.

Numerous factors contribute to obesity, but the least of them is genetics.

Myth #3 – You Can Out-Exercise a Bad Diet

The myth that you can eat whatever you want and burn the calories with exercise is completely false and makes no sense if you understand how the human body works.

If you think you can exercise your way to weight loss, you’re in for a big disappointment if you treat yourself to a post-workout sugar-laden smoothie, muffin or other “healthy” snack. You can’t just suck back some Gatorade to quench your thirst after your 30 minutes on the treadmill.

If you’re relying on exercise to lose weight without changing your diet, you’re setting yourself up for failure. You can change your diet and lose weight, but if you exercise and keep your diet the same, you may gain some muscle, improve endurance and be healthier overall, but you won’t shed many pounds.

Put this into perspective: If you drink just one 20-ounce soda, you’ll have to walk four-and-a-half miles to burn it off. If you consume one super-sized fast-food meal, you’ll have to run four miles a day for one whole week to burn it off. If you eat that every day, you have to run a marathon every single day to burn it off.

You simply cannot exercise your way out of a bad diet. Yes, exercise is extremely important, but to lose weight and keep it off you need to couple exercise with a healthy diet filled with plenty of plant foods, healthy fats and protein.

Myth #4 – Fat Makes You Fat

Here’s another pet peeve: Eating fat makes you fat.

Fat is not a four-letter word! Eating fat not only doesn’t make you fat, it’s critical to health and weight loss.

Studies comparing a high-fat diet that is identical in calorie count to a high-sugar diet had totally different effects on metabolism. The higher-fat diet caused people to burn an extra 300 calories a day. That’s the equivalent of running for an hour without doing any exercise.

Dietary fat actually speeds up your metabolism, while sugar slows it down. The right kinds of fat cool down inflammation, while sugar fuels it.

In studies of animals that ate identical calorie diets of either low-fat (high-sugar) or higher-fat and protein diets showed that higher-sugar diets led to more fat deposition and muscle loss, while the higher-fat and protein diets led to more muscle mass and fat loss. Keep in mind they were eating exactly the same number of calories.

The right fats are actually your cells’ preferred fuel, especially those fats called medium-chain triglycerides (MCTs) that come from foods like coconut oil and coconut butter.

Yes, stay away from trans fats, but good fats like extra-virgin olive oil, coconut butter, avocado, nuts, seeds and nut butters keep us full and lubricate the wheels of our metabolism. Please stop fearing fat!

I’ve created a plan to reset your body and move toward your best self that incorporates movement, supplementation and above all, food and dietary fats .

The Eat Fat, Get Thin program is a 21-day plan designed to support weight loss, maximize energy and mental clarity and kick start your health.

Thousands of people all over the world have completed this program, and the results have been astonishing. If you’re tired of typical calorie-deprivation diets that don’t work, I highly recommend joining our Eat Fat, Get Thin January challenge.

If you liked this information, please share it with your friends and family on Facebook and Twitter. And, help me continue to clear up nutrition and health confusion by submitting your questions to drhyman.com. Let’s spread real truth and inspire others!

Wishing you health & happiness,

Mark Hyman, MD

It's quite a long post from Jason Fung, but one you maybe interested to read.

"Insulin, first discovered in 1921, revolutionized the treatment of type 1 diabetes. Dr. Banting licensed insulin to pharmaceutical companies without a patent because he believed that this life saving drug for T1D should be made available to everybody who needed it. So, why is insulin so hard to afford today?

Only three pharmaceutical companies manufacture insulin in the United States – Eli Lilly, Sanofi and Novo Nordisk. In 2012, it is estimated that insulin alone cost the US health care system $6 billion. How can they make so much money from a century old product? In 2013, according to firecepharma.com, the best selling drug for diabetes was…. Lantus, a long acting form of insulin. So, after all the research of the past 95 years, the biggest money-makin’, mama-shakin’ drug was insulin? Yes, sir. Worldwide, this drug alone made $7.592 billion. That’s billion with a B. Oh, but the news gets better for Big Insulin. Out of the top ten, various insulins also ranked #3, 4, 6,7,9, and 10. Holy patent extensions Batman! A full seven of the top ten drugs for diabetes are insulin – a drug close to a century old. It’s like your 95 year old grandfather beating LeBron James at basketball.

Tweaking the insulin molecule allows additional patents and cheaper generic medications can be kept at bay. That this clearly violates Dr. Banting’s original intention doesn’t matter. There is no clear evidence that these newer insulins are any more effective than the old standards. While there are some theoretical benefits, the outcomes in T2D have only worsened even as these newer insulins became more widely prescribed. Hiking prices is another lucrative technique. From 2010 to 2015, the price of newer insulins rose from 168- 325%. Without generic competition, there is clearly collusion between the companies to keep prices high. After all, shareholders must be kept happy and the CEO needs a private jet.

At the time of insulin’s discovery, T2D, while still relatively rare, had few treatments available. Metformin, the most powerful of the biguanide class of medications, was discovered shortly after insulin and described in the scientific literature in 1922. By 1929, its sugar lowering effect was noted in animal studies, but it was not until 1957 that it was first used in humans for the treatment of diabetes.

It entered the British National Formulary in 1958, and entered Canada in 1972. It was not FDA approved in the United States until 1994 due to concerns about lactic acidosis. It is now the most widely prescribed diabetes drug in the world.

The sulphonylurea drug class was discovered in 1942 were introduced in 1956 in Germany. By 1984, more powerful second generation SUs were introduced in the United States. These drugs stimulated the pancreas to release more insulin, which reduced blood sugars. There were many side effects, including severe hypoglycemia, but they did prove effective at lowering blood sugars. For decades, these two drug classes were the only oral medications available for the treatment of T2D.

Even while the number of blood pressure and cholesterol medications were exploding, the oral hypoglycaemic drug class was mired in a rut. There was simply no money to be made for drug companies. The numbers of patients were too small, and the benefits of these drugs were dubious. But things were soon to change.

In 1977, the Dietary Guidelines for Americans were introduced to an unsuspecting American public and dietary fat was public enemy #1. The subsequent high carbohydrate intake would have unintended consequences and the obesity epidemic soon bloomed. Following like a love-sick puppy was the epidemic of T2D.

In 1997, the American Diabetes Association lowered the blood sugar definition of type 2 diabetes, instantly rendering as many as 1.9 million more Americans as diabetic.

Pre-diabetes underwent a similar change in definition in 2003. This would label 25 million more Americans as pre-diabetic. With growing numbers, the business case for the development of diabetic medications changed completely. While there is broad consensus that pre-diabetes is best treated with lifestyle changes, advocacy groups soon embraced the notion of drug therapy. The guidelines have been lowered so much that, by 2012, the prevalence of diabetes in American adults was 14.3% and prediabetes 38%, adding up to 52.3% of americans being either pre-diabetic or diabetic. This was now the new normal. It was more common to have pre-diabetes or diabetes than it was to have normal blood sugars. Diabetes is the new black.

By 1999, the diabetes economy was primed to boom. In 1999, rosiglitazone and pioglitazone were approved by the FDA for the treatment of T2D. They have subsequently fallen into disuse due to concerns about provoking heart disease and bladder cancer. But it hardly mattered. The dam had burst. From 2004- 2013, no less than thirty new diabetes drugs were brought to market.

By 2015 sales of diabetes drugs had reached $23 billion, more than the combined revenue of the National Football League, Major League Baseball, and the National Basketball Association. This was big time business.

While these drugs all lowered blood sugars, clinically important outcomes, such as reducing heart attacks or strokes, blindness, or other complications of the disease, were not improved. The entire diabetes industry revolved around reducing high blood sugars instead of actually helping patients. The disease was one of increased insulin resistance, yet treatments were based upon lowering blood sugars instead. We were treating symptoms, instead of the actual disease.

Follow the Money

In 2003 the American Diabetes Association changed the definition of pre-diabetes adding an additional 46 million adults to its ranks. In 2010, the definition was further broadened by the use of the Hgb A1C. Ostensibly to help with early diagnosis and treatment, it is perhaps no coincidence that 9 of 14 outside experts on this panel worked in various capacities with the giant pharmaceutical companies that made diabetes medications and stood to reap an unending stream of money.

While individual members were paid millions of dollars, the association itself reaped more than $7 million in 2004 from its pharmaceutical ‘partners’. By 2012, more than 50% of the American population would be considered either diabetic or pre-diabetic. Mission accomplished. Cha ching. The market for drug consumption had been created."

Do please go across to Dr Fung's site to finish reading the article

https://intensivedietarymanagement.com/diabetes-economy-t2d/

Oh don't get me wrong, fitness and exercise are good for many things, just not the #1 strategy for losing weight. And especially bad when you continually carb up and drink "sports drinks" full of sugar.

Many people on low carb/Paleo diets find they suddenly have a lot more energy and need to find ways of using it. At ny nadir on low fat, I attacked the hedge with my petrol trimmer, including waving it above my head, but could only manage about ten minutes before I was totally exhausted and took a couple of hours to recover. I also gained around 15kg, all on my gut.

Obviously these two events were not unconnected, just not in the way Conventional Wisdom suggests. Likewise losing the weight and regaining the energy both came principally from changing my diet. While kids are being trained to follow the Eatwell Plate, no amount of exercise is going to help anyone who is not carb-tolerant.