Caffeine protects against Alzheimer's

In oxygen-deprived mice

Recent studies have linked caffeine consumption to a reduced risk of Alzheimer's disease, and a new University of Illinois study may be able to explain how this happens.

"We have discovered a novel signal that activates the brain-based inflammation associated with neurodegenerative diseases, and caffeine appears to block its activity. This discovery may eventually lead to drugs that could reverse or inhibit mild cognitive impairment," said Gregory Freund, a professor in the U of I's College of Medicine and a member of the U of I's Division of Nutritional Sciences.

Freund's team examined the effects of caffeine on memory formation in two groups of mice—one group given caffeine, the other receiving none. The two groups were then exposed to hypoxia, simulating what happens in the brain during an interruption of breathing or blood flow, and then allowed to recover.

The caffeine-treated mice recovered their ability to form a new memory 33 percent faster than the non-caffeine-treated mice. In fact, caffeine had the same anti-inflammatory effect as blocking IL-1 signaling. IL-1 is a critical player in the inflammation associated with many neurodegenerative diseases, he said. "It's not surprising that the insult to the brain that the mice experienced would cause learning memory to be impaired. But how does that occur?" he wondered.

The scientists noted that the hypoxic episode triggered the release of adenosine by brain cells. "Your cells are little powerhouses, and they run on a fuel called ATP that's made up of molecules of adenosine. When there's damage to a cell, adenosine is released," he said. Just as gasoline leaking out of a tank poses a danger to everything around it, adenosine leaking out of a cell poses a danger to its environment, he noted.

The extracellular adenosine activates the enzyme caspase-1, which triggers production of the cytokine IL-1β, a critical player in inflammation, he said. "But caffeine blocks all the activity of adenosine and inhibits caspase-1 and the inflammation that comes with it, limiting damage to the brain and protecting it from further injury," he added.

Caffeine's ability to block adenosine receptors has been linked to cognitive improvement in certain neurodegenerative diseases and as a protectant against Alzheimer's disease, he said.

"We feel that our foot is in the door now, and this research may lead to a way to reverse early cognitive impairment in the brain. We already have drugs that target certain adenosine receptors. Our work now is to determine which receptor is the most important and use a specific antagonist to that receptor," he said.

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Hypoxia/Reoxygenation Impairs Memory Formation via Adenosine-Dependent Activation of Caspase 1

Gabriel S. Chiu1 et al.

Abstract

After hypoxia, a critical adverse outcome is the inability to create new memories. How anterograde amnesia develops or resolves remains elusive, but a link to brain-based IL-1 is suggested due to the vital role of IL-1 in both learning and brain injury. We examined memory formation in mice exposed to acute hypoxia. After reoxygenation, memory recall recovered faster than memory formation, impacting novel object recognition and cued fear conditioning but not spatially cued Y-maze performance. The ability of mice to form new memories after hypoxia/reoxygenation was accelerated in IL-1 receptor 1 knockout (IL-1R1 KO) mice, in mice receiving IL-1 receptor antagonist (IL-1RA), and in mice given the caspase 1 inhibitor Ac-YVAD-CMK. Mechanistically, hypoxia/reoxygenation more than doubled caspase 1 activity in the brain, which was localized to the amygdala compared to the hippocampus. This reoxygenation-dependent activation of caspase 1 was prevented by broad-spectrum adenosine receptor (AR) antagonism with caffeine and by targeted A1/A2A AR antagonism with 8-cyclopentyl-1,3-dipropylxanthine plus 3,7-dimethyl-1-propargylxanthine. Additionally, perfusion of adenosine activated caspase 1 in the brain, while caffeine blocked this action by adenosine. Finally, resolution of anterograde amnesia was improved by both caffeine and by targeted A1/A2A AR antagonism. These findings indicate that amygdala-based anterograde amnesia after hypoxia/reoxygenation is sustained by IL-1β generated through adenosine-dependent activation of caspase 1 after reoxygenation.

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The Nitrate and Nitrite Myth: Another Reason not to Fear Bacon

Goodie!  I have been having bacon 'n eggs for breakfast most mornings for many years.  Now I can rest easy

Bacon has been long considered unhealthy due to the use of nitrates and nitrites in the curing process. Many conventional doctors, and well-meaning friends and relatives, will say you’re basically asking for a heart attack or cancer by eating the food many Paleo enthusiasts lovingly refer to as “meat candy”.

The belief that nitrates and nitrates cause serious health problems has been entrenched in popular consciousness and media. Watch this video clip to see Steven Colbert explain how the coming bacon shortage will prolong our lives thanks to reduced nitrates in our diets.

In fact, the study that originally connected nitrates with cancer risk and caused the scare in the first place has since been discredited after being subjected to a peer review. There have been major reviews of the scientific literature that found no link between nitrates or nitrites and human cancers, or even evidence to suggest that they may be carcinogenic. Further, recent research suggests that nitrates and nitrites may not only be harmless, they may be beneficial, especially for immunity and heart health. Confused yet? Let’s explore this issue further.

It may surprise you to learn that the vast majority of nitrate/nitrite exposure comes not from food, but from endogenous sources within the body. (1) In fact, nitrites are produced by your own body in greater amounts than can be obtained from food, and salivary nitrite accounts for 70-90% of our total nitrite exposure. In other words, your spit contains far more nitrites than anything you could ever eat.

When it comes to food, vegetables are the primary source of nitrites. On average, about 93% of nitrites we get from food come from vegetables. It may shock you to learn that one serving of arugula, two servings of butter lettuce, and four servings of celery or beets all have more nitrite than 467 hot dogs. (2) And your own saliva has more nitrites than all of them! So before you eliminate cured meats from your diet, you might want to address your celery intake. And try not to swallow so frequently.

All humor aside, there’s no reason to fear nitrites in your food, or saliva. Recent evidence suggests that nitrites are beneficial for immune and cardiovascular function; they are being studied as a potential treatment for hypertension, heart attacks, sickle cell and circulatory disorders. Even if nitrites were harmful, cured meats are not a significant source, as the USDA only allows 120 parts per million in hot dogs and bacon. Also, during the curing process, most of the nitrite forms nitric oxide, which binds to iron and gives hot dogs and bacon their characteristic pink color. Afterwards, the amount of nitrite left is only about 10 parts per million.

And if you think you can avoid nitrates and nitrites by eating so-called “nitrite- and nitrate-free” hot dogs and bacon, don’t be fooled. These products use “natural” sources of the same chemical like celery and beet juice and sea salt, and are no more free from nitrates and nitrites than standard cured meats. In fact, they may even contain more nitrates and nitrites when cured using “natural” preservatives.

It’s important to understand that neither nitrate nor nitrite accumulate in body. Ingested nitrate from food is converted into nitrite when it contacts our saliva, and of the nitrate we eat, 25% is converted into salivary nitrite, 20% converted into nitrite, and the rest is excreted in the urine within 5 hours of ingestion. (3) Any nitrate that is absorbed has a very short half-life, disappearing from our blood in under five minutes. (4) Some nitrite in our stomach reacts with gastric contents, forming nitric oxide which may have many beneficial effects. (5, 6) You can listen to my podcast “Does Red Meat Increase Your Risk of Death?“ for more information on this topic.

In general, the bulk of the science suggests that nitrates and nitrites are not problematic and may even be beneficial to health. Critical reviews of the original evidence suggesting that nitrates/nitrites are carcinogenic reveals that in the absence of co-administration of a carcinogenic nitrosamine precursor, there is no evidence for carcinogenesis. (7) Newly published prospective studies show no association between estimated intake of nitrite and nitrite in the diet and stomach cancer. (8) Nitric oxide, formed by nitrite, has been shown to have vasodilator properties and may modulate platelet function in the human body, improving blood pressure and reducing heart attack risk. (9, 10, 11) Nitrates may also help boost the immune system and protect against pathogenic bacteria (12, 13, 14)

So what do we take from this? There’s no reason to fear nitrates and nitrites in food. No reason to buy nitrate-free, uncured bacon. No reason to avoid cured meats in general, particularly those from high quality sources. In fact, because of concerns about trichinosis from pork, it makes a lot more sense in my opinion to buy cured bacon and other pork products. I do.

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