Robert back packing in Laos showing metabolic syndrome

 Age Successfully describes how to age without having all of the  infirmities blamed on age. It describes how the author did it wrong, did  the research and now at 85 years old lives a life with minimum  infirmities. It describes how to minimize, and in most cases eliminate diabetes, heart disease, stroke, degraded cognition, fall fractures,  diabetic amputations, cancer, and vision loss. More than one half of all medical care is needed because of lifestyle diseases. There is no need to be in that half. The book covers why calorie restriction, exercise and reduction of dietary fat does not cure obesity and what does. How to cure prediabetes and type 2 diabetes. How to minimize the chance of Alzheimer’s disease. Understand and prevent what causes high blood pressure, low HDL and high A1c. (High LDL is not bad) 

The image is of Robert backpacking in Laos in 2016 with his son-in-law, Andy. It shows his metabolic syndrome belly. His two heart operations were in early 2017

Lifelong Plan for long and healthy life:

Kick the caffeine habit and only use Caffeine for times when extra physical or mental demands are expected. It is important to stay hydrated without over drinking and losing too many minerals. Everyone should eliminate unsaturated vegetable fats like corn oil, soybean oil and other seed oils. 

Everyone  should  reduce sweets to one small serving a day and limit fruits to one serving the size of your fist.  These count in the one serving: sugar soft drinks, cookies,  candy, sugar containing cereals,  packaged foods with any sugar,   ketchup, salad dressing with sugar.
Limit carbohydrates to 50% of calories or less.  

    
Use MCT oil or olive oil for salads only. Cook with saturated fats Lard, Butter, Coconut oil or Tallow. Eat at least one serving of cruciform vegetables at least 2 times each week.
Schedule at least 8 hours of sleep and eliminate blue light at least two hours before bed time. 
Use a multivitamin, magnesium, calcium with vitamin D, Turmeric, vitamin D3 and vitamin C supplements. Consume some fish or take an Omega 3 supplement or both.
Exercise  at least three times a week. This exercise should include: aerobic, weight bearing and three short periods of high intensity exercise.

Do some intermittent fasting at least once a week. The easiest fasting is 18 hours by only eating from Noon to 6:00 PM each day. Consume at least 20 grams of fiber per day. Consume the recommended amount of protein Limit fruit to one serving a day
For someone that is not diabetic, prediabetic or obese simply doing what is suggested above should be all that is necessary for leading a long life without unnecessary infirmities. Prediabetics and Diabetics need to further reduce carbohydrates. 

How to lose weight without a great deal of willpower, pain, or suffering

Calorie  restriction fails to reduce weight 99% of the time. The metabolic system will slow down to compensate for calorie restriction, at the same time, step up the production of ghrelin, the hunger hormone, and  decrease the hormones that would reduce hunger.

Exercise in  moderation is an excellent way to be healthy. It is only a minimally effective weight-loss strategy. Exercise increases hunger, and moderate exercise does not significantly increase the metabolic rate.  Long-duration high-intensity exercise can be harmful.

Fructose is in all added sugars. (table sugar, honey, maple syrup, high fructose corn syrup, and agave)  Fructose increases the production of ghrelin. Fructose can not be used  by the body for energy and must be converted to fat by the liver. Fat from the liver is stored in a fatty organ surrounding the intestines; this belly fat is the most visible sign of metabolic syndrome. Metabolic syndrome leads to heart disease, fatty liver disease, cancer, diabetes,  and Alzheimer’s.

Weight loss requires fat burning and can only happen when the level of insulin in the body is low. Sugars, starches, and excess proteins keep insulin high.

Steps to effective weight loss:

Eliminate all added sugars: no cookies, fruit juices (not even orange juice), candy, cakes, pies, condiments with added sugar (catsup), etc. Limit  fruit to one serving a day. Learn to read food labels to avoid buying  foods with added sugar.

Eat a high-fat, low carbohydrate diet.  Saturated fats are the best. (See life401.com March 19, 2025)  Fat will reduce apatite. Unfortunately many obese people lose the signal from fat to stop eating. Eat about 0.4 grams of protein per day  for each pound of target weight. For those over 65, eat 0.5 grams of  additional protein. Read food labels and do the math.

Set a realistic target. A reduction of 10% of your current weight is  realistic; after hitting this target and maintaining this weight, you  may want to set a new target. Unrealistic targets can lead to disappointment and giving up.

Do not snack. Snacks keep insulin levels high and prevent fat burning.

Use intermittent fasting. Pick a time window and only eat within that window. I fast from 6:00 PM until Noon the next day, an 18 hour fast.  Everyone is different; you may only be able to fast for 13 hours a day.

Stay  busy.  Everyone has found that they have been active on some project and missed a meal. If you follow the above, you will quickly lose  several pounds of water. After the first few pounds, the loss will be  fat. It will be slow, but it is essential to stay with it. A slow loss over a long time is the most healthful. Cycling loss, gain, loss, gain  is deadly. 

The basics of eliminating sugar was known in 1863 Banting, W. (1863). Letter on Corpulence, Addressed to the Public.  https://archive.org/details/letteroncorpulen00bant/page/10/mode/2up

Phillips https://alzres.biomedcentral.com/articles/10.1186/s13195-021-00783-x

The Ketogenic Diet and Alzheimer's Disease H Hersant 1, G Grossberg
https://pubmed.ncbi.nlm.nih.gov/30554068/

 Prevent or cure Alzheimer's disease

For Alzheimer's disease prevention and cure:  Read the Cunnane paper to understand the principles of changing the brain from glucose fuel to ketone fuel. We need to provide medium-chain fatty acids that can be converted to ketones and reduce glucose availability to force the conversion. The conversion happens when in or partially in ketosis. This treatment is based on the theory that the brain loses its ability to use glucose and does not lose its ability to use ketones for energy. The brain can grow more cells and synapses, but this is slow. This treatment must be started before a significant part of the brain is lost. If Cunnane is right, amyloid and tau proteins are brain scar tissue and not the cause of the problem.

Any attempt to cure Alzheimer's will only work if the subject has a reason to be intellectually active. There needs to be a life purpose or life goals. If the subject is simply in a retirement facility waiting to die, they have no incentive to improve their intellectual capacity. Without a life purpose, why not have Alzheimer's? In later stages, it is less stressful. The Alzheimer's cure will cure diabetes first. 

The first step is to reduce insulin that would will prevent ketone metabolism.

Take two tablespoons of MCT oil three times a day. MCT oil can have a laxative effect and can cause digestive upset. It may need to be added incrementally. Use coconut oil, lard, or Tallow for cooking.

Take 2 grams of turmeric (Curcumin) daily to clear amyloid plaque proteins from the brain. 

Eat two eggs a day to increase cholesterol availability.

Eliminate added sugars to reduce A1c and Eliminate potatoes, sweet potatoes, rice, corn, bread, carrots, beets, and other starchy foods.

Eat 50 grams of protein a day. This quantity is about two McDonalds patties. An egg has 7 grams of protein. Nuts are from 18 to 25% protein, and beans are 8 to 12% protein.

Reduce carbohydrates to less than 10% of calories while maintaining fiber intake.

Physical exercise and mental exercise are needed to exercise the brain. Both physical and psychological exercise encourage new brain cell formation and synapse formation.

Use intermittent fasting to clear inactive proteins and mitochondria. I recommend 18 hours a day fasting. I fast from 6:00 PM to Noon the next day.

This diet may be needed for months to restore lost cognitive function slowly. Because glucose metabolism is lost, this diet may be needed forever.

Cunnane, S. C., Courchesne-Loyer, A., St-Pierre, V., Vandenberghe, C., Pierotti, T., Fortier, M., … Castellano, C. A. (2016). Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease. Annals of the New York Academy of Sciences, 1367(1), 12–20. https://doi.org/10.1111/NYAS.12999

Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease

Matthew C. L. Phillips https://alzres.biomedcentral.com/articles/10.1186/s13195-021-00783-x

The Ketogenic Diet and Alzheimer's Disease H Hersant 1, G Grossberg

https://pubmed.ncbi.nlm.nih.gov/30554068/

Anderson,  P. (n.d.). Gum Disease Bacteria a New Treatment Target for AD?  Retrieved October 2, 2022, from  https://www.medscape.com/viewarticle/963574?uac=362670CN&faf=1&sso=true&impID=3824361&src=wnl_edit_tpal#vp_2

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(O'Donnell et al., 2014)Mente, A., O'Donnell, M., & Yusuf, S. (2021, June 1). Sodium and health: Another challenge to the current dogma. European Heart Journal. Oxford University Press. https://doi.org/10.1093/eurheartj/ehaa1093

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NIH. (n.d.). What Happens to the Brain in AD? | National Institute on Aging. Retrieved October 2, 2022, from https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease

(O'Donnell et al., 2014)

Mente, A., 

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Understanding Alzheimer's Disease 

Robert Harrison Black

​Alzheimer's disease (AD) is named after Dr. Alois Alzheimer. In 1906, Dr. Alzheimer documented changes in the brain tissue of a woman who had died at age  55 of a rare mental illness.

 In AD, as neurons are injured and die throughout the brain, connections between networks of neurons may break down, and many brain regions begin to shrink. By the final stages of AD, this process—called brain atrophy—is widespread, causing significant brain volume loss. (NIH, no date)

AD has been studied with microscopes and other scientific equipment. I looked at AD from a global perspective. AD was rare and is now common and becoming a pandemic. As a good scientist, I ask what has changed.

Our genetics have not changed.
We are getting older, which would explain part of the increase.
We sit more, watching TV or on a computer.
Smoking has declined. I could not find a biochemical link that would increase AD by reducing smoking.
We are consuming a great deal of added sugars. These added sugars include fructose. (Seneff et al., 2010)
We have decreased our consumption of sodium chloride (salt)
We are consuming more inflammatory omega-6 oils.

Life Style Studies:

         Livingston, writing in Lancet, said less education, hypertension,  hearing impairment, smoking, obesity, depression, physical inactivity,  diabetes, low social contact, excessive alcohol consumption, traumatic brain injury, and air pollution account for around 40% of worldwide dementias. These dementias could theoretically be prevented or delayed.  The potential for prevention is high and might be higher in low-income and middle-income countries where more dementias occur. (Livingston et  al., 2020)

       The items on Livingston's list match recommendations for a healthy heart and a lower cancer risk. These recommendations, and those from Baumgart (below), will increase the likelihood of a better life; everyone should follow these recommendations. However, these recommendations show how to reduce the risk of AD but do not show how to reverse AD progression.  

         Melzer et al. stress the need for micronutrients such as vitamins and minerals to maintain health. They also recommend optimizing macronutrients, but this recommendation was not further developed. They assert nutritional status as the most critical modifiable factor regulating the gut microbiota at different time points across the lifespan and under various health conditions. The brain-gut link is identified as essential. (Melzer, Manosso, Yau, Gil-Mohapel, &  Brocardo, 2021)

 I have reviewed many clinical studies that describe the Mediterranean diet. They are not consistent, but they have two things in common. They are low in added sugars and use olive oil, not inflammatory vegetable oils like soybean. (Baumgart et al., 2015) Appendix A explains why the term Mediterranean Diet is not useful.

Both gingivitis and E. coli bacteria have been implicated in AD. When I first read the gingivitis study, I thought: Of course, AD patients forget to brush their teeth. Both of these bacteria live on dead tissue. The dead brain cells provide nourishment for these bacteria. (Anderson, 2021)  (Zhan et al., 2016) Zahn has noted the fibers in E. coli and their similarity to those in AD. These bacteria may be more a symptom than a cause. In both studies, healthy brains had some gingivitis and E. coli bacteria.

Sugar consumption:

AD increase correlates with the increased intake of added sugars; these include sucrose, high fructose corn syrup, maple syrup, agave, honey, and others. The average American ate only 2 pounds of added sugar a year two hundred years ago. (NH Health, 2014)

Year      Consumption

1814 -   2 pounds per year

1970 -   123 pounds per year

2014 -   152 pounds per year

Table 1 Added sugar consumption per year.

In one year, we consume about 152 pounds of added sugar or nearly 3 pounds per week.

Increased sugar consumption is linked to AD. Both correlation and biochemistry show this link.

There is an agreement in the literature that brain glucose uptake is impaired in AD. Can cognitive decline be delayed if this brain energy defect is partly corrected or bypassed early in the disease? The principal ketones  (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's primary physiological alternative fuel to glucose. These two of many studies in mild-to-moderate AD have shown that these brain ketones are as useful to the brain as glucose in healthy age-matched controls. (Cunnane et al., 2016) (Juby 2022) Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis with medium-chain triglyceride oil has a beneficial effect on cognitive outcomes in mild-to-moderate AD and mild cognitive impairment. (July 2022)

Dietary Fats:

We are also consuming omega-6 seed oils. These oils cause inflammation that damages all tissue, including the heart, brain, kidneys, and pituitary.

Oil Type                 1814          1909       1999       Percent increase

Soybean                  0              0.01        11.6        116,300

Canola1                   0              0.01        0.8          16,700

Safflower3              0              0.04        0.05        25

Cottonseed              0                0.4        0.31      −21
 

Table 2 Consumption of omega-6 oils in Kilograms per person per year

 Omega  6 oil consumption has also tracked AD. Something changes in the brain  from being able to use glucose for fuel to needing β-hydroxybutyrate and  acetoacetate. The cause of this change in brain metabolism has not been  found. Double-blind and biochemical studies are required to know what  these oils do to us.

 In addition omega-6 fats are unsaturated  and more likely to become oxidized in LDL cholesterol. These oxidized  LDL particles cannot be used in cells and will continue circulating,  causing systemic inflammation. Oxidized LDL will also stick to the walls  of the arteries, causing plaques. Fats sticking to the walls of arteries  causes a cascade of events that lead to clots. This cascade consists of continued accumulation of fatty deposits, attempts by white blood cells  to clear the oxidized LDL from the arterial walls, inflammation signals  from the white cells, inflammation of the blood vessels that have the  deposits, and finally, the buildup of deposits and the formation of  clots. Ravnskov and Kromer focused on heart disease, but the findings  may also apply to the even finer capillaries in the brain.  (Ravnskov et  al., 2014) (Kromer, 2018)

Omega 3 fatty acids, primarily from fish, have been shown to reduce the probability of AD (Ma, 2020). Olive  oil is low in omega-6 fatty acids, which may be why some Mediterranean  diets show positive results.

Studies:

Kane et al. have done a compensative study of attempts to cure AD. Some of the studies provided temporary symptom relief, but none prevented the progress of the disease. "We found mostly low-strength evidence that a  wide variety of interventions had little to no benefit for preventing or  delaying age-related cognitive decline." (Kane, M.D., Butler, Ph.D.,  MBA, & Fink, M.D., MPH, 2017) Ketogenic and medium-chain triglyceride diets were not on the list of treatments studied by Kane et al..

A high-fat ketogenic diet can achieve nutritional ketosis by providing 20–70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate or by ketone esters. (de la Rubia et al., 2020) Insulin blocks the metabolism of fats and promotes the storage of body fat. Carbohydrates must be limited to use eight- and ten-carbon fatty acids, octanoate, and decanoate.  Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD  must target how the underlying problem of deteriorating brain fuel supply can be corrected or delayed.

There are many patients on a ketogenic diet to prevent seizures. The ketogenic diet is high in fat,  adequate in protein, and very low in carbohydrates. A typical ketogenic diet for controlling seizures consists of 70% to 80% fats, 20% proteins,  and 5% to 10% carbohydrates. Doctors typically recommend the keto diet to treat epilepsy in children of all ages, including infants. Ketogenic diets are usually not preferred by adults because the limited food  choices make the diet hard to maintain. The keto diet has also been used  in other neurological conditions, including AD and an autism spectrum  disorder. (Caraballo, n.d.)

Taylor et al. found that AD could be  reversed using medium-chain triglycerides and a ketogenic diet. Their  trial only succeeded with subjects with very mild or mild cognitive  impairment. With the more severely cognitively impaired, the dropout rate was 100%. These studies have a problem with the subject's  unwillingness to stay on the diet or the heavy caregiver burden being  too hard. (Taylor, Sullivan, Mahnken, Burns, & Swerdlow, 2018)

Melzer et al. recognized the loss of the ability of the brain to use glucose and the effectiveness of medium-chain triglycerides in the pathology of  AD. This revelation was not further developed. (Melzer, Manosso, Yau,  Gil-Mohapel, & Brocardo, 2021)

Coconut oil is high in medium-chain fatty acids, easily converted to beta-hydroxybutyrate and acetoacetate; our brains can use these instead of glucose. Many studies have been done on both coconut oil and medium-chain triglyceride oil. I reference one by W M A D B Fernando (Fernando, 2015). All of the studies with medium-chain triglyceride oil show positive results, and most studies with coconut oil show positive results.

The study by Xu et al. showed a significant (p < 0.01) reduction in the AD assessment scale scores used by Xu. There was a 2.62 improvement for the medium-chain triglyceride oil. And a 2.57 decrease in the score for the placebo over 30 days. They used medium-chain triglycerides (MCT) oil

 with canola oil as a control. The TC, HDL-C, β-hydroxybutyrate, and acetoacetate concentrations were significantly higher in the MCT group than in the placebo group. (Xu et al., 2020)

Roy et al. used multimodal imaging to show that a ketogenic intervention in mild cognitive impairment improved the dorsal attention network's functional, metabolic, and structural integrity. This network enables us to interact with the environment. The 6-month ketogenic medium chain triglyceride supplementation increased functional connectivity within the dorsal attention network as a direct function of improved brain energy status due to higher ketone availability. Attention also improved as a function of enhanced functional connectivity. Analysis of the comprehensive structural map of neural connections in the brain revealed increased fiber density within the dorsal attention network following ketogenic medium-chain triglyceride consumption. (Roy et al.,  2022)

Rebello et al. "Consumption of 56 g/day of medium chain  triglycerides for 24 weeks increases serum ketone concentrations and  appears to be a candidate for larger randomized control trials in the  future that quantify the modulation of cognitive function through  supplementation with ketone precursors in patients with mild cognitive  mild impairment." (Rebello et al., 2015)

Mental exercises have a minimal long-term effect in preventing a decline in cognitive function.  The researchers found that mental stimulation improved memory and thinking test scores for those with dementia, equivalent to a six to nine-month delay in worsening symptoms. Some studies found dementia patients who engaged in such activities had increased feelings of well-being and a better quality of life, including improved communication and interactions with those around them. They were,  however, no better able to care for themselves or function independently. (Woods, Aguirre, Spector, & Orrell, 2012)

Changes from baseline scores for exercise program patients showed a slower decline than in patients receiving routine medical care. No effect was observed for behavioral disturbance, depression, or nutritional assessment scores. (Rolland et al., 2007)

Drugs for AD:

Drugs have not been shown to reverse AD. The recently approved drug  Aducanumab is one in a long line of failed drugs that prevent or reduce amyloid beta plaques. Aducanumab was approved over the objection of the scientific review panel. Trials of Aducanumab have shown mixed results.  It will likely fail because the prevention of amyloid beta has consistently failed to delay or reverse AD. Other drugs stimulate the brain and temporarily show delay or reversal. None  have been shown to delay or reverse AD permanently.

Tampi, Forester, &  Agronin also reviewed the clinical trials of Aducanumab.  They did not find evidence of a long-term benefit from Aducanumab. They  showed why the Drugs Advisory Committee of the FDA voted, with ten  members against it and one member uncertain that it was not reasonable  to consider the evidence of clinical benefit from Study 302 as primary  evidence of the effectiveness of aducanumab. (Tampi, Forester, &  Agronin, 2021)

Until recently, in the United States, only five treatments were approved by the US FDA for neurocognitive symptoms of  AD. These include three cholinesterase inhibitors (donepezil,  galantamine, and rivastigmine), one N-methyl-D-aspartate receptor antagonist (memantine), and a combination of donepezil and rivastigmine.  The first four drugs are also licensed in the European Union. In the  United States, a fixed-dose combination of donepezil and memantine was approved in 2014 for treating individuals with moderate to severe AD  dementia who are stable on donepezil. These drugs reduce symptoms but do not slow the progression of AD. (Tampi, Forester, & Agronin, 2021)

Mehta et al. studied the failure of AD drugs. The article was titled "Why do  trials for AD drugs keep failing?" They reviewed drugs that were anti-amyloid monoclonal antibodies, used gamma-secretase to decrease the  production of amyloid, controlled tau protein, enhanced neurochemicals,  and blocked antihistamines. All were failures. (Mehta, O'Donnell, and  Yusuf, 2021)

The Indian spice curcumin is a principal constituent of the spice turmeric. Recent research on amyloid-β and curcumin has  revealed that curcumin prevents amyloid-β aggregation and crosses the  blood-brain barrier (BBB), reaches brain cells, and protects neurons  from various toxic insults of aging and amyloid-β in humans." (Reddy et  al., 2018) Molecular variations of curcumin may also be effective against AD. 

Salt:

"There is evidence that high salt intake is associated with poor cognition. However,  findings are mixed due to poor methodological quality and the studies'  heterogeneous dietary, analytical, and cognitive assessment methods and design. Reduced sodium intake may be a potential intervention target. High-quality prospective studies and clinical trials are  needed." (Mohan et al., 2020)

O'Donnell found that a salt intake  between 3 and 6 grams per day was associated with a lower risk of death.  This quantity is what we naturally consume. The lowest level of AD was  when consuming salt to taste. This level of salt intake is between 3 to 5  grams per day. Low salt may be part of the problem; I did not find any  double-blind clinical studies on salt and AD.  (O’ Donnell et al. 2014)

Discussion:

Correlation is not causation; we must have good clinical studies and biochemical mechanisms.

Genetics  have been studied concerning AD. Some genetics have been linked to an  increased risk of AD, but no studies show a new gene is spreading in the  adult population.

An aging population has more time for AD  symptoms to become apparent. We are getting older, which would explain at least part of the increase. Also, more people are being diagnosed  earlier.

Our increasingly sedentary lifestyle is likely a cause of a portion of the increase. Intellectual stimulation has been shown to slow the development of AD. By delaying the diagnosis, some people who would have been diagnosed with AD may die of other causes before diagnosis.

I did not find a link to smoking cessation.

This linkage is also true of Omega-6 oils. Both correlation and biochemistry show this link. We do not have a way to determine what percentage is caused by sugar and what percentage is Omega 6 oils.

Eliminating carbohydrate consumption to obtain at least partial ketosis and providing medium-chain triglycerides successfully stopped the progression and partially reversed cognitive decline.  (De la Rubia Ortí  JE, 2020) Age Successfully Second Edition provides a diet that meets the requirements of De la Rubia Ortí JE to prevent and reverse cognitive decline (Black, 2020). This diet prevents further neuron death. New brain cells are added slowly to the brain in older subjects. The brain is plastic, and some recovery can be made by brain reorganization. To live a normal life, including personal hygiene, the diet must be started  before significant neuron death has occurred.

Conclusion:

Diet  is the only treatment shown to work in the long run.