Mice Fed Fatty Diets For 30 Weeks Show Signs of Depression, Anxiety, And Alzheimer's

[Vince]

The cheap, readily available, highly processed food we're consuming too much of is bad for us. An interesting new mouse study has backed up the enduring hypothesis that high fat and sugar diets and cognitive decline such as Alzheimer's are linked.

"Obesity and diabetes impair the central nervous system, exacerbating psychiatric disorders and cognitive decline. We demonstrated this in our study with mice," says University of South Australia neuroscientist and biochemist Larisa Bobrovskaya.

The team were looking for a mouse model that can tell us more about the intersection between Alzheimer's disease, type two diabetes and obesity, and oh boy did they find it.

Mice Fed Fatty Diets For 30 Weeks Show Signs of Depression, Anxiety, And Alzheimer's

The cheap, readily available, highly processed food we're consuming too much of is bad for us.

www-sciencealert-com.cdn.ampproject.org

 

[tareload]

The cheap, readily available, highly processed food we're consuming too much of is bad for us. An interesting new mouse study has backed up the enduring hypothesis that high fat and sugar diets and cognitive decline such as Alzheimer's are linked.

"Obesity and diabetes impair the central nervous system, exacerbating psychiatric disorders and cognitive decline. We demonstrated this in our study with mice," says University of South Australia neuroscientist and biochemist Larisa Bobrovskaya.

The team were looking for a mouse model that can tell us more about the intersection between Alzheimer's disease, type two diabetes and obesity, and oh boy did they find it.

Mice Fed Fatty Diets For 30 Weeks Show Signs of Depression, Anxiety, And Alzheimer's

The cheap, readily available, highly processed food we're consuming too much of is bad for us.

www-sciencealert-com.cdn.ampproject.org

I wonder why these types of macros keep getting called a "high fat" diet instead of SAD (standard American diet). Now I gotta go look up the macros in the paper. I am going to guess there was a lot of sugar in there with the fats. Curious.

Note, usually bad to mix concentrated sugar plus fat in meals unless you know what you are doing for a specific purpose.

 

[FunkOdyssey]

I wonder why these types of macros keep getting called a "high fat" diet instead of SAD (standard American diet). Now I gotta go look up the macros in the paper. I am going to guess there was a lot of sugar in there with the fats. Curious.

Note, usually bad to mix concentrated sugar plus fat in meals unless you know what you are doing for a specific purpose.

Specific foods and substances are the problem, not macronutrients. A soda and a serving of fruit may have the same amount of sugar. Foods deep-fried in vegetable oil may have the same fat content as a grass-fed ribeye steak. The health impacts couldn't be more divergent.

 

[tareload]

Foods deep-fried in vegetable oil may have the same fat content as a grass-fed ribeye steak

What foods are you referring to here in terms of frying?

Is that frying a turkey or frying some potatoes?

Depending on whether former or later the macros could be very different than ribeye.

 

[FunkOdyssey]

What foods are you referring to here in terms of frying?

Is that frying a turkey or frying some potatoes?

Depending on whether former or later the macros could be very different than ribeye.

Lets say it's deep-fried chicken so the macronutrients are similar. The oxidized vegetable oil will turbocharge artherosclerosis development. Have you seen the animal studies where they reheat oils 5-10-20x and the artherosclerosis scales perfectly with the number of times the oil was heated? Crazy stuff.

Meanwhile, I had a nearly perfect coronary calcium scan after eating three years of a carnivore + fruit style diet (90% or more daily calories from beef). Three arteries with a score of 0 and one with a score of 2.

 

[BigTex]

I think science has also determined that genetics go a long way to determine in you are going to have Alzheimer’s Disease. If you carry the ε4 allele of the ApoE gene, then you are at a greater risk for Alzheimer’s disease. It is thought that people with the ApoE gene also have difficulty with glucose metabolism. One group of researchers sought out to find answers by comparing a standard diet to a high-fat, low-carb diet (keto) in mice with Alzheimer’s disease. The authors found that the brains of the mice that were fed a high-fat, low-carb diet had lower levels of beta-amyloid plaque compared to the standard diet fed mice. This suggests that a ketogenic diet may have the ability to reverse plaque accumulation in Alzheimer’s patients. Again, we go back to glucose metabolism. But researchers went further and found that ketones actually reversed the adverse effects that the beta-amyloid plaque causes.

As Readalot was saying the typical American diet of high fat and high GI carbohydrates is not so healthy for most. Especially for those who carry the ε4 allele of the ApoE gene that re more prone to Alzheimer's.

 

[Phil Goodman]

Lets say it's deep-fried chicken so the macronutrients are similar. The oxidized vegetable oil will turbocharge artherosclerosis development. Have you seen the animal studies where they reheat oils 5-10-20x and the artherosclerosis scales perfectly with the number of times the oil was heated? Crazy stuff.

Meanwhile, I had a nearly perfect coronary calcium scan after eating three years of a carnivore + fruit style diet (90% or more daily calories from beef). Three arteries with a score of 0 and one with a score of 2.

Agree with this 100%. In simplest terms I think it comes down to inflammation. Vegetable oils and processed sugars are terrible for inflammation, as well as all the chemicals pumped into processed foods. Just look at what has happened to physical and mental health in the Western World when these things became staples in our diets.

And it is interesting that they highlight “high fat” in the diets of those mice but then specifically say it includes high sugar as well and don’t give the breakdown for the diet. There is a clear push to get humans to eat less meat which will just make our health even worse, and these types of studies will probably be used to push that agenda.

 

[BigTex]

This data came from a speaking engagement by Dr. Jeff Volek. I use this in my nutrition class every semester. As you can see in the early 70's there was a push to eat less meet, thus reducing saturated fats. As we took the protein out of our diets we increased consumption of carbohydrates, mostly in the form of simple carbohydrates. Interesting enough, the rate of obesity and diabetes followed the exact same path as did the increase in carbohydrate consumption

 

[Guided_by_Voices]

I'd say this study is totally bogus just based on the title. Fats are not one thing any more than gasoline, diesel fuel and propane are the same thing. Similar studies (such as the one that tried to link "fat" to breast cancer) were found to be meaningless years ago when the composition of the mouse chow was analyzed. As has been pointed out many times here, the Bredesen protocol is the place to start for any discussion of dementia, as well as overall health. Another example of why scientists cannot be trusted and the scientific method is actively avoided.

 

[BigTex]

Samuel T. Henderson, Chapter 40 - Ketosis in Mild Cognitive Impairment and Alzheimer’s Disease, Editor(s): Colin R. Martin, Victor R. Preedy, Diet and Nutrition in Dementia and Cognitive Decline, Academic Press, 2015, Pages 447-456, ISBN 9780124078246,

https://doi.org/10.1016/B978-0-12-407824-6.00040-9.

Abstract
Aging is accompanied by decreased cerebral glucose metabolism (DCGM). Regional DCGM can be detected in patients with mild cognitive impairment and Alzheimer’s disease well before clinical signs of memory impairment are evident, and offers a possible target for intervention. One approach is to supplement the brain with ketone bodies. Ketone bodies include β-hydroxybutyrate, acetoacetate, and acetone. In adults, ketone bodies are normally produced during prolonged fasting or when a low-carbohydrate diet is consumed. Ketosis has demonstrated efficacy in human clinical trials of Alzheimer’s disease and mild cognitive impairment. Much of the benefit of ketosis can be attributed to increased mitochondrial efficiency and the ability to supplement the brain’s normal reliance on glucose. Research into the therapeutic potential of ketosis represents a promising, low-risk intervention that can be implemented early in the disease process and offers an exciting new area of study in age-associated cognitive decline.


Davis JJ, Fournakis N, Ellison J. Ketogenic Diet for the Treatment and Prevention of Dementia: A Review. J Geriatr Psychiatry Neurol. 2021 Jan;34(1):3-10. doi: 10.1177/0891988720901785. Epub 2020 Jan 30. PMID: 31996078.

Abstract​

Dementia (major neurocognitive disorder) is an increasingly common syndrome with a significant burden on patients, caregivers, the health-care system, and the society. The prevalence of dementia will certainly continue to grow as the US population ages. Current treatments for dementia, though, are limited. One proposed nonpharmacologic approach for the delay or prevention of dementia is the use of a ketogenic diet. The ketogenic diet was originally employed to treat refractory epilepsy and has shown promise in many neurologic diseases. It has also gained recent popularity for its weight loss effects. Several preclinical studies have confirmed a benefit of ketosis on cognition and systemic inflammation. Given the renewed emphasis on neuroinflammation as a pathogenic contributor to cognitive decline, and the decreased systemic inflammation observed with the ketogenic diet, it is plausible that this diet may delay, ameliorate, or prevent progression of cognitive decline. Several small human studies have shown benefit on cognition in dementia with a ketogenic diet intervention. Future, large controlled studies are needed to confirm this benefit; however, the ketogenic diet has shown promise in regard to delay or mitigation of symptoms of cognitive decline.

 

[tareload]

Have you seen the animal studies where they reheat oils 5-10-20x and the artherosclerosis scales perfectly with the number of times the oil was heated? Crazy stuff.

Examples... A little plunge into rodent world:

Reheated Palm Oil Consumption and Risk of Atherosclerosis: Evidence at Ultrastructural Level

<i >Background</i>. Palm oil is commonly consumed in Asia. Repeatedly heating the oil is very common during food processing. <i >Aim</i>. This study is aimed to report on the risk of atherosclerosis due to the reheated oil consumption. <i >Material and Methods</i>. Twenty four male Sprague...

www.hindawi.com

Consumption of repeatedly heated soy oil increases the serum parameters related to atherosclerosis in ovariectomized rats - PubMed

Repeated heating of soy oil may promote lipid peroxidation. Oxidized unsaturated fatty acids may contribute to the pathogenesis of atherosclerosis, especially in estrogen-deficient states. This study was performed to explore the deleterious effects of repeatedly heated soy oil on the development...

pubmed.ncbi.nlm.nih.gov

Then there's the fun one:

Oxidized Fatty Acids Promote Atherosclerosis Only in the Presence of Dietary Cholesterol in Low-Density Lipoprotein Receptor Knockout Mice

Abstract. Studies suggest that heated oils contribute to the presence of oxidized components in the circulating lipoproteins and to the development of atheroscl

academic.oup.com

And not to be left out:

Low-carb diets linked to atherosclerosis and impaired blood vessel growth — Harvard Gazette

Even as low-carbohydrate/high-protein diets have proven successful at helping individuals rapidly lose weight, little is known about the diets’ long-term effects on vascular health. Now, a study led by team…

news.harvard.edu

Long term vascular effects of keto diet in humans? Probably depends. Still trying to figure that one out. My TC is 200 / HDL is about 62 / triglycerides 38 on modified keto with veggies. Lipoprofile panel looks good.

My main strategy is to keep all the oxandrolone and stanozolol in the fridge and just look at it occasionally when I get the urge - but not use it. Cardiologist thinks I eat too much fatty fish, too many vegetables, and exercise too much. That much healthy stuff is not healthy. Where's the moderation?

I'd have to bet on @BigTex 's comment that genes go a long way.

 

[tareload]

I don't have access to article mentioned in title of thread but here's an example of "high fat" diet sometimes used in the rodent literature:

A Ketogenic Diet Is Protective Against Atherosclerosis in Apolipoprotein E Knockout Mice

AbstractObjectives. A ketogenic diet (KD) positively impacts cardiovascular disease (CVD) risk factors yet its effect on atherosclerosis, the main cause of CVD,

academic.oup.com

Methods
Seven-week-old male Apoe−/− mice, a model for human atherosclerosis, were fed ad libitum (%kcal) KD (81-fat, 1-carbohydrate, 18-protein; n = 4) or HF (40-fat, 42-carbohydrate, 18-protein; n = 5). After 4, 8 and 12 weeks, plasma was collected and used to (1) quantify beta-hydroxybutyrate levels (OH-But) by a colorimetric assay; or (2) assess systemic inflammation, a key feature associated with atherosclerosis, using a panel of inflammatory cytokines; or (3) explore diet-driven changes in levels of atherosclerosis-relevant metabolites using a targeted metabolomic approach by triple quadrupole mass spectrometry. At the endpoint, mice were euthanized and their perfusion-fixed aortas were subjected to 3-D analysis by magnetic resonance imaging to quantify the extent of atherosclerosis. Data were reconstructed using Matlab and segmented to obtain atherosclerotic plaque volumes using Avizo 9.0.


High fat diet lingo in the rodent literature is code for standard American diet (2:2:1 ratio of % of kcal for F/C/P). Ketogenic diet (KD) above is actually the true high fat diet !

 

[tareload]

Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis - Signal Transduction and Targeted Therapy

In addition to their use in relieving the symptoms of various diseases, ketogenic diets (KDs) have also been adopted by healthy individuals to prevent being overweight. Herein, we reported that prolonged KD exposure induced cardiac fibrosis. In rats, KD or frequent deep fasting decreased...

www.nature.com

Ketogenic Diet Suppressed T-Regulatory Cells and Promoted Cardiac Fibrosis via Reducing Mitochondria-Associated Membranes and Inhibiting Mitochondrial Function

Ketogenic diet (KD) is popular in diabetic patients but its cardiac safety and efficiency on the heart are unknown. The aim of the present study is to determine the effects and the underlined mechanisms of KD on cardiac function in diabetic cardiomyopathy (DCM). We used db/db mice to model DCM...

www.hindawi.com

Hey, hold on, you told me keto diet is protective against atheroschlerosis! What the hell, where did this heart fibrosis stuff come from?

 

[tareload]

Not a perfect transfer function for humans.

Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice​

 

[FunkOdyssey]

And not to be left out:

Low-carb diets linked to atherosclerosis and impaired blood vessel growth — Harvard Gazette

Even as low-carbohydrate/high-protein diets have proven successful at helping individuals rapidly lose weight, little is known about the diets’ long-term effects on vascular health. Now, a study led by team…

news.harvard.edu

Look at the actual contents of the diets from that study:

They didn't vary the fat content of the diet at all between the western diet and the low-carb diet. What they did was replace sugar and corn starch with massive amounts of casein. If anything, this study implicates casein as an agent of atherosclerosis in mice, and it is literally worse than pure sugar. I wouldn't find that too surprising as casein is often associated with inflammation, especially the A1 version of beta-casein.

 

[tareload]

Look at the actual contents of the diets from that study:

View attachment 23569

They didn't vary the fat content of the diet at all between the western diet and the low-carb diet. What they did was replace sugar and corn starch with massive amounts of casein. If anything, this study implicates casein as an agent of atherosclerosis in mice, and it is literally worse than pure sugar. I wouldn't find that too surprising as casein is often associated with inflammation, especially the A1 version of beta-casein.

True and great point. My point was an example on the terminology of "high fat" thrown around and you gotta be careful as that many times is the "WD" from the table you just posted.

But your comments do reinforce your point above that macros ain't the end all / be all.

 

[BigTex]

I don't have access to article mentioned in title of thread but here's an example of "high fat" diet sometimes used in the rodent literature:

A Ketogenic Diet Is Protective Against Atherosclerosis in Apolipoprotein E Knockout Mice

AbstractObjectives. A ketogenic diet (KD) positively impacts cardiovascular disease (CVD) risk factors yet its effect on atherosclerosis, the main cause of CVD,

academic.oup.com

Methods
Seven-week-old male Apoe−/− mice, a model for human atherosclerosis, were fed ad libitum (%kcal) KD (81-fat, 1-carbohydrate, 18-protein; n = 4) or HF (40-fat, 42-carbohydrate, 18-protein; n = 5). After 4, 8 and 12 weeks, plasma was collected and used to (1) quantify beta-hydroxybutyrate levels (OH-But) by a colorimetric assay; or (2) assess systemic inflammation, a key feature associated with atherosclerosis, using a panel of inflammatory cytokines; or (3) explore diet-driven changes in levels of atherosclerosis-relevant metabolites using a targeted metabolomic approach by triple quadrupole mass spectrometry. At the endpoint, mice were euthanized and their perfusion-fixed aortas were subjected to 3-D analysis by magnetic resonance imaging to quantify the extent of atherosclerosis. Data were reconstructed using Matlab and segmented to obtain atherosclerotic plaque volumes using Avizo 9.0.


High fat diet lingo in the rodent literature is code for standard American diet (2:2:1 ratio of % of kcal for F/C/P). Ketogenic diet (KD) above is actually the true high fat diet !

As you mentioned, there lies the problem. The carbs were the problem all along.

Jeff Volek, Ph.D., R.D. wrote in a study he did comparing low fat to keto, two factors influence the amount of fat coursing through your veins. The first, of course, is the amount of fat you eat. But the more important factor is less obvious. Turns out, your body makes fat from carbohydrates. It works like this: The carbs you eat (particularly starches and sugar) are absorbed into your bloodstream as sugar. As your carb intake rises, so does your blood sugar. This causes your body to release the hormone insulin. Insulin's job is to return your blood sugar to normal, but it also signals your body to store fat. As a result, your liver starts converting excess blood sugar to triglycerides, or fat.

In this study that Volek lead, scientists placed overweight men and women on either a low-carb or low-fat diet. Those who followed the low-carb diet consumed 36 grams of saturated fat per day (22 percent of total calories), which represented more than three times the amount in the low-fat diet. Yet despite this considerably greater intake of saturated fat, the low-carb dieters reduced both their number of small, dense LDL cholesterol and their HDL/LDL ratio to a greater degree than those who ate a low-fat diet. In addition, triglycerides decreased by 51 percent in the low-carb group--compared with 19 percent in the low-fat group.

 

[Guided_by_Voices]

Look at the actual contents of the diets from that study:

View attachment 23569

They didn't vary the fat content of the diet at all between the western diet and the low-carb diet. What they did was replace sugar and corn starch with massive amounts of casein. If anything, this study implicates casein as an agent of atherosclerosis in mice, and it is literally worse than pure sugar. I wouldn't find that too surprising as casein is often associated with inflammation, especially the A1 version of beta-casein.

There is a big difference between PUFA fats (really bad in high amount and if oxidized) and non-PUFA fats (generally good unless paired with high amounts of low-quality carbs.) Also the carbs are very different if they are a-cellular (i.e. flour, which is bad) vs. in whole form. Also not that mice AFAIK have an enzyme to break down grains which humans don't have. The fact that they don't specify this is a huge red flag.

 

[Guided_by_Voices]

Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis - Signal Transduction and Targeted Therapy

In addition to their use in relieving the symptoms of various diseases, ketogenic diets (KDs) have also been adopted by healthy individuals to prevent being overweight. Herein, we reported that prolonged KD exposure induced cardiac fibrosis. In rats, KD or frequent deep fasting decreased...

www.nature.com

Ketogenic Diet Suppressed T-Regulatory Cells and Promoted Cardiac Fibrosis via Reducing Mitochondria-Associated Membranes and Inhibiting Mitochondrial Function

Ketogenic diet (KD) is popular in diabetic patients but its cardiac safety and efficiency on the heart are unknown. The aim of the present study is to determine the effects and the underlined mechanisms of KD on cardiac function in diabetic cardiomyopathy (DCM). We used db/db mice to model DCM...

www.hindawi.com

Hey, hold on, you told me keto diet is protective against atheroschlerosis! What the hell, where did this heart fibrosis stuff come from?

It would be interesting to know what people deep in the science such as Volek/D'agostino think of the idea that ketones alone are damaging to the heart, since this seems to fly in the face of other evidence to the contrary. I vaguely recall other data suggesting that non-stop keto for extended periods could create problems, and this makes sense since there is really no historical precedent for that, but my understanding is that the heart actually 'prefers" ketones, at least in the short run. Also, I didn't see any indication of the contents of the diet, so again, the PUFA issue could confound the results.

 

[BigTex]

Great article here on the importance of limiting PUFAS (polyunsaturated fatty acids) in your diet. PUFAs are very high in Omega 6 fatty acids, these are know to cause inflammation in the body which increase c-reactive protein levels. This can result in many of our different health issues including CHD and cancer. They typical American diet consist of 16:1 Omega 6 to Omega 3. A much more healthy ratio is from 4:1 to 1:1.

PUFA's: The Worst Thing For Your Health You Eat Everyday

People fuss over salt, sugar & cholesterol yet no one talks about PUFA's. PUFA's are often regarded as 'healthy fats'. But when we look at the effect they have on our health & waistline it is clear we have our priorities mixed up. PUFA's are much more damaging than the commonly regarded 'bad' foods

www.alexfergus.com