Jan
04
2020

Preserving Youthful Power

Dr. Christopher W. Shade (PH.D.) presented a lecture in Las Vegas on Dec.13, 2019 talking about preserving youthful power. The presentation was at the 27th Annual World Congress on Anti-Aging Medicine and his title was “Building Youthful NAD+ Power with Precursors, Sirtuin-Activating Compounds, and Methylation support”.

In the first place, nicotinamide adenine dinucleotide (NAD+) is a signalling molecule between the DNA of the nucleus of cells and the energy producing mitochondria that reside in the cells. The exact nature of the interaction is described in this review article. It describes how stress leads to a depletion of NAD+ and sirtuins, and causes accelerated aging. On the other hand, calorie restriction and exercise lead to increased production of NAD+, activation of sirtuins and longevity.

Details about low NAD+ activity

It is important to realize that when NAD+ is below a critical level the following disease states can develop. First, in the brain it is Alzheimer’s disease and neurodegenerative disease. Second, in the eyes macular degeneration and keratoconjunctivitis sicca can develop. Third, severe plaque-type psoriasis can occur in the skin. Fourth, the pancreas develops hyperinsulinemia and metabolic syndrome. Fifth, type 2 diabetes can make your muscles weak. Sixth, sarcopenia with loss of muscle mass and cardiovascular disease in the heart can also develop. Seventh, the liver reacts to the metabolic syndrome by causing hepatic steatosis. Metabolic syndrome causes inflammatory cytokines in the fatty tissue. Eighth, the lungs react by developing chronic obstructive pulmonary disease. Ninth, your blood can get endotoxin-induced inflammation and sepsis from bacteria. A lack of NAD+ causes all of these negative changes simultaneously in the body.

In fact, when a person exercises regularly, uses intermittent fasting as a tool of calorie restriction and takes supplements of NAD+ all of these negative processes stop and sirtuins are activated restoring the body to a more youthful condition.

Summary about the effects of NAD+

In other words, NAD+ is important for cardiometabolic health, energy balance, liver health, immune health and cognitive health. NAD+ is also involved in maintaining the membrane polarity of cell walls. The blood /brain barrier and the gut/blood barrier are also kept intact by NAD+. In addition, NAD+ is involved in detoxification and control of the action of free radicals. It also is important to control Inflammation. For these reasons, it is not a surprise that people with normal NAD+ function will be healthier than those who have a problem with this.

Sugar reduces NAD+ to NADH

It is important to note that scientists could show in animal models and in humans that sugar overconsumption leads to the reduction of NAD+ to NADH. All of the negative effects described above for low NAD+ are then coming true. NADH is a reduced and disabled form of the oxidized NAD+. In essence, this substance has no biological action.

Energy metabolism

Biochemists have determined with regard to the energy metabolism of mitochondria that there are three occasions where enzymes are dependent on NAD+. Without NAD+ the energy-providing oxidative metabolism in mitochondria would not take place. As NAD+ is lower in older age, this explains why an aging population has less energy. In addition, as we age, the number of mitochondria per cell is decreasing. That is to say that an aging population has less energy than youthful people.

Other factors that are important in preserving youthful power

The AMPK signalling pathway

AMPK stands for 5′ AMP-activated protein kinase. This is an enzyme that consists of three protein portions. In humans it is expressed in liver, brain and muscle tissue. It provides energy in the liver by fatty acid oxidation. In muscles it stimulates glucose uptake and fatty acid oxidation. AMPK also inhibits cholesterol synthesis, lipogenesis and triglyceride synthesis. Fasting and exercise can stimulate AMPK production, which in turn will stimulate SIR1 genes and NAD+ production. This is especially happening in muscle tissue. To put it another way, there are a close-linked metabolic reactions between NAD+, AMPK and sirtuins.

Balance between AMPK, NAD+ and methylation

Given the right circumstances this can lead to detoxification, longevity and energy. This is what intermittent fasting and exercise can do for you. AMPK needs high NAD+ levels to give you all of the benefits. But NAD+ must be balanced with methylation. This is a somewhat difficult subject to explain, but the link explains it in somewhat technical terms. In other words, with a balance of the body’s biochemistry the person is healthy. When there is a disbalance, you get sick.

Practical application how to supplement for preserving youthful power

Dr. Shade asked the rhetorical question: how can we achieve a balance between NAD+ and methylation?

His answer is to supplement with the following supplements.

  • Trimethylglycine (Betaine) 2‐5g/day
  • Vitamin B2: 10‐30mg/day
  • SAMe or methylcobalamin 1000‐3000mcg/day
  • Measure Homocysteine as marker of methylation; if it is low, the methylation pathway is normal and there is balance.

Next: how to we raise NAD+? The answer is by cardio-metabolic blending.

  • Berberine and quercetin (they are respiratory chain modulators)
  • Resveratrol, silymarin and lipoic acid (they are liver kinase B1 activators)
  • Resveratrol or pterostilbene and quercetin (they are sirtuin activators)
  • Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) 200- 400 mg per day
  • Trimethylglycine (Betaine) 2-5 grams per day and methylcobalamin, B2, and others (methylation support)
Preserving Youthful Power

Preserving Youthful Power

Conclusion

It is difficult to describe energy flow in biochemical terms. Dr. Christopher W. Shade did exactly that in a lecture he gave at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas on Dec.13, 2019. The key for preserving youthful power is to balance the metabolism that occurs in the nucleus of the body cells with the metabolism taking place in the mitochondria. The mitochondria are the energy producers, but the steering of this occurs through the metabolic products from the cell nucleus. NAD+ plays a key role in our energy metabolism. But there is an interplay with AMPK, which stands for 5′ AMP-activated protein kinase. Sirtuin genes interact with these messenger molecules as well and this is where longevity comes in.

Longevity through sirtuin stimulation

Sirtuins are longevity genes that help us get more energy for a longer period of time. Regular exercise stimulates this complex biochemistry giving us extra NAD+ for energy. Intermittent fasting also stimulates sirtuins, which adds to the extra energy and gives us longevity. This is not a bad deal when you look at it from a distance. We can achieve a lot preserving our energy through an active life style. Supplements can be an auxiliary measure, but they are not effective enough without positive lifestyle choices.

Dec
29
2018

Fasting Mimicking Diet Is Very Relevant For Health And Longevity

Several speakers in Las Vegas said that the fasting mimicking diet is very relevant for health and longevity. This happened on day 1 of the 26th Annual A4M World Congress 2018 in Las Vegas.

What were the findings that are relevant?

Dr. Longo has done a lot of animal experiments with intermittent fasting and studying longevity. He repeated what he has learnt over the years from animal experiments and from research on humans. Here are the results that he shared already at last year’s Anti-aging Conference in Las Vegas.

Effects of fasting mimicking diet

  • Obesity diminishes, because of the weight loss effect due to missing calories.
  • Diabetes: insulin resistance becomes lower and blood sugar levels drop.
  • High blood pressure reduced: many patients were able to reduce their medications or discontinue them
  • Pain conditions improve as all kinds of pain disappears, an effect for which there is no explanation at this point
  • Autoimmune diseases like MS and rheumatoid arthritis improve, likely because of the effect of increased stem cell circulation
  • Prevention of heart attacks and strokes because of reduction of LDL, triglycerides and CRP
  • Cancer cure rates improve by protecting normal cells and the bone marrow
  • Longevity improved in mice with a 3-fold increase of their life span. Telomere length in humans was increased. Increased stem cells will find defective areas that need repair. This effect leads to less disease in older age.

Increased life span, less heart attack and cancer rates

We know from these animal experiments that mice have a threefold increase in life span. But when heart attack rates and stroke rates improve in humans, cancer cure rates improve and telomere length in humans increase, there is strong evidence that it increases human life expectancy as well. It may take another 10 to 20 years before we have better statistics about the real survival advantage on this diet versus the Standard American diet. But what we know now is a significant start.

Patients on chemotherapy and FMD have much better healing rates than controls

The lecture by Dr. Longo on Dec. 13, 2018 did provide more human data. Patients undergoing chemotherapy tolerate and survive chemotherapy much better when combined with the fasting mimicking diet (FMD). The human data is very similar to the previous mouse model data. This human research was done at the Charité Hospital in Berlin, Germany. Dr. Longo is starting to engage in clinical trials by partnering with physicians, but the publication of this will take several years. In the meantime the FMD is an effective way to rejuvenate on an ongoing basis. Since last year I underwent 12 courses of 5-day FMD every month. Dr. Longo says that even 3 to 4 courses of FMD per year would have a lasting rejuvenating effect.

About the right food intake and getting enough sleep

Dr. La Valle gave a talk in the afternoon of the first conference day where he pointed out several important things. He started his talk by saying that North Americans eat the wrong foods, they eat too much of it and they often eat it at the wrong time (in the middle of the night when the body wants to rest). This can interfere with our diurnal hormone rhythm, which in turn will eventually lead to inflammation in the body. Fasting overnight rests our hormone receptors so they are fully active the following day.

Preventing Alzheimer’s disease

Dr. La Valle praised the FMD as being able to elevate brain derived neurotropic factor. Newer research is pointing at the importance of this factor for preventing Alzheimer’s disease and Parkinson’s disease. He pointed out that the FMD is a good start to change other things in a patient’s life. Such things like exercise, bioidentical hormone replacement and taking vitamins and supplements. All of these all in combination will build up a patient’s health.

More human data about anti-aging

The internist, Dr. Kurt Hong said that he is seeing 200 patients every week. He has done clinical studies on various forms of fasting. The FMD, he said he liked best as it is easy to do (5 days out of one month 500 calories on each of the FMD days). Dr. Hong has seen amazing improvements in patients with MS, Hashimoto’s disease and Crohn’s disease. His talk concentrated on how fasting improved the metabolic syndrome, improved inflammation in the body and improved immune diseases. The FOXO pathway involves transcription factors that are important to regulate cell death (apoptosis). A variant of FOXO3 is responsible for longevity in humans and has been found in centenarians.

Dr. Hong pointed out that self-cleaning (autophagy) is an important rejuvenation process in the body. The FMD stimulates this process. In a 2017 study Dr. Longo and Dr. Hong compared 100 regular patients with 100 patients on the FMD. Only the patients on the FMD showed that the body weight came down. In addition the blood pressure came down as well and the pluripotent stem cells in the blood were up. So, the FMD has a positive effect on various organ systems without any medication. The strongest effect of the FMD would be in the age group of 20 to 40 for anti-aging purposes as it stimulates stem cell production and elongates telomeres.

Fasting and women’s health

Dr. Felice Gersh gave a talk about the effects of fasting on women’s health. She pointed out how important estrogen is in a woman for every organ system. All of the major organ systems including the skin have estrogen receptors. Estrogen stimulates the metabolism. It stimulates the immune system by stimulating macrophages that also have estrogen receptors. In menopause less estrogen production leads to a lack of energy, because the mitochondria are no longer stimulated as they were before. Estrogen also stimulates sirtuins, which is important for anti-aging. Studies with the FMD have shown that estrogen production is re-stimulated in women.

Dr. Joel Kahn was another speaker in the afternoon. He talked about how important the FMD is for cardiovascular health. He does not think that coronary artery surgeries and stents will suddenly get abandoned, but he thinks that the FMD is a powerful tool to delay arteriosclerosis in the arteries. This will delay coronary artery lesions from developing and will add life. In his opinion 40 to 60 year old patients should start using the FMD to prevent cardiovascular disease.

Aging drives chronic disease

Sebastian Brandhorst, PhD pointed out that if we stay active and eat healthy, we will age well. The US is the only country on earth where the life expectancy goes down after there was an initial health gain in the past.

Yeast, worms, flies and mammals follow a nutrient-sensing pathway. That means when food is not around, starvation increases resistance to a variety of toxins. One important aspect of the FMD is the observation that it protects the body against the toxic effects from chemotherapy. FMD and chemotherapy combined almost completely blocked progression of breast cancer in mice. Further studies showed that cytotoxic T cells were responsible for stopping cancer growth. When antibodies against T cells were administered, the beneficial cytotoxic T cell effects against cancer were wiped out. In humans the same protective effect of the FMD was observed. The FMD combined with chemotherapy gave the best survival data in cancer patients.

Fasting Mimicking Diet Is Very Relevant For Health And Longevity

Fasting Mimicking Diet Is Very Relevant For Health And Longevity

Conclusion

The fasting mimicking diet (FMD) was ranking very prominently among last year’s anti-aging conference in Las Vegas. Several speakers of this year’s anti-aging conference pointed to the health supporting effect of the FMD. It is now evident that the previous findings in animal research are also true in humans. Missing at this time are prolonged clinical trials that analyze the mechanisms of why the FMD works so well. In the meantime everybody can safely use FMD 5 days out of every month, which will rejuvenate your system by gradually prolonging pluripotent stem cell activation and telomere lengthening. It is just a matter of time when the missing links will be filled in.

More info: intermittent fasting may benefit health.

Nov
24
2018

Intermittent Fasting May Benefit Health

There is a lot of discussion about the fact that intermittent fasting may benefit health. But there are a confusing variety of intermittent fasting schedules. This makes it difficult to compare notes regarding the specific effect of an intermittent fasting diet. Generally speaking when there is some form of calorie restriction, our body goes into a survival mode of operating. These types of diets provide enough nutrients to not get into malnutrition, but at the same time they may stimulate sirtuins, particularly SIR2. This is thought to be associated with longevity.

Various forms of fasting

Eating after 5 PM

The Taylors in the CNN article eat the same amount of calories, but they only eat after 5PM. They claim to have more energy and be less vulnerable to infections. They also think that they feel younger than in the past.

Fasting every other day

This was an observation in the 1980’s to help rats live longer compared to rats that have food available every day. Recent experiments on mice showed similar results: calorie restriction in whatever form leads to prolonged life and health.

Human fasting mimicking diet

A 2017 study on 100 humans divided this group into half. One half ate any food as they wished. The other half consumed only 800 to 1100 calories for 5 days of each month as a fasting mimicking diet. The experimental group had lower fasting blood sugars; cholesterol, triglycerides and other heart disease markers went down. The IGF-1 markers for various cancers also went down. The experimental group lost abdominal fat, but preserved lean body mass. Valter Longo, who co-authored the clinical study said that a human trial on longevity would almost be impossible to design, and would cost “a hundred million dollars or more. But if you look at the data from our trial … it would be hard to see how they would not live longer.”

5:2 diet

Patients are allowed to eat what they want for 5 days of the week, but then they restrict their diet for 2 consecutive days. The control group had no restriction of calories. The 5:2 experimental group had better glucose control and loss of abdominal fat than the control group.

Fasting can help you live-longer

Experts on calorie-restricted diets tell us that there is a switch in metabolism from burning glucose as fuel to using ketones as fuel. Extended periods of exercise will also cause a switch to using ketones as fuel. Repeated cycling from fasting to eating may also benefit our brain function. Intermittent fasting will help us cope better with stress and disease. But Dr. Longo says that this is only one aspect. He found in his research that with intermittent calorie restriction there is a multi-system regeneration going on. For instance, damaged white blood cells are depleted, stem cells are activated, blood sugar control is improved and heart risk factors are being controlled. Dr. Longo mentioned that when tissues are healthy and functional, risk factors for disease decrease.

Mechanisms behind longevity

Dr. Longo explained in detail the complex aging pathways that involve three components, IGF-1, mTOR and PKA. When lifestyle choices stimulate these genetic markers, accelerated aging is the consequence. But with the inhibition of those markers longevity will happen. Here are some of the effects on the body of a fasting mimicking diet.

  • Obesity diminishes, because of the weight loss effect due to missing calories.
  • Diabetes: insulin resistance becomes lower and blood sugar levels drop.
  • High blood pressure reduced: many patients were able to reduce their medications or discontinue them
  • Pain conditions improve as all kinds of pain disappears, an effect for which there is no explanation at this point
  • Autoimmune diseases like MS and rheumatoid arthritis improve, likely because of the effect of increased stem cell circulation
  • Prevention of heart attacks and strokes because of reduction of LDL, triglycerides and CRP
  • Cancer cure rates improve by protecting normal cells and the bone marrow
  • Longevity improved in mice with a 3-fold increase of their life span. Telomere length in humans was increased. Increased stem cells will find defective areas that need repair. This effect will open up a new chapter in medicine.
Intermittent Fasting May Benefit Health

Intermittent Fasting May Benefit Health

Conclusion

Calorie restriction is a powerful method to rejuvenate the body. Surprisingly 5 days out of one month of a calorie restricted fasting mimicking diet is all that is necessary to improve the body’s metabolism. Telomeres get increased, damaged white blood cells are removed and stem cells get stimulated. But weight loss, improvement of pain perception and cardiovascular risk reduction take place as well. In mice longevity was significantly prolonged, but this needs to still be shown in humans.

One can think of an intermittent fasting mimicking diet as a kind of internal cleansing. Following this it is easier to restart the metabolism with clean ingredients.

So far I have followed 11 courses of the fasting mimicking diet. But I don’t buy boxes of 300.00 USD every month. Instead I count calories myself, keep the diet balanced and buy the ingredients in the health food store. I agree that the fasting mimicking diet seems to be effective and it helps to keep my body mass index under control.

Mar
11
2017

Obesity And Diabetes Can Cause Cancer

Dr. Nalini Chilkov gave a talk about how obesity and diabetes can cause cancer. The original title was “Integrative Cancer Care, Increased Rates of Cancer and Cancer Mortality Associated with Obesity and Insulin Resistance, Nutraceutical and Botanical Interventions”. She presented her talk at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended.

In the following I will present a brief summary of her lecture.

Obesity is a major risk factor for cancer

Obesity causes 14% of all cancer deaths in men and 20% of cancer deaths in women.  This link explains this in more detail. The following 15 cancers related to obesity in terms of causation. They are: colon cancer, gastric cancer, gallbladder cancer, ovarian cancer, breast cancer, liver cancer, uterine cancer, endometrial cancer, rectal cancer, pancreatic cancer, cervical cancer, non-Hodgkin’s lymphoma, renal cancer, multiple myeloma and esophageal cancer.

The American Society of Clinical Oncology reported about a meta-analysis involving 82 studies. This involved more than 200,000 women with breast cancer. The researchers compared premenopausal and postmenopausal women who were obese or normal weight. Premenopausal, obese breast cancer women had a 75% increase in mortality compared to the normal weight breast cancer group. In comparison with the normal weight group the postmenopausal group of obese breast cancer women showed a 34% increase of mortality.

With obese prostate cancer patients there is a similar observation. Obese patients have a more aggressive prostate cancer on the Gleason score and the cancer is in a more advanced stage at the time of diagnosis.

Diabetes increases mortality from cancer

Obesity is a common risk factor for both cancer and diabetes. But diabetes by itself is also increasing mortality of several cancers. In a consensus report details of the relationship between cancer and diabetes have been discussed in detail. The following cancers have been identified to have an increased risk of diabetes: pancreatic, gastric, esophageal, colorectal, liver, gallbladder, breast, ovarian, endometrial, cervical, urinary bladder, renal, multiple myeloma and non-Hodgkin’s lymphoma.

A meta-analysis suggests that cancer patients who are diabetic have a 1.41-fold increased risk of dying compared to those cancer patients who have normal blood sugars. Dr. Chilkov explained in detail what the various mechanism are that account for the faster cancer growth in obese and diabetic patients. High insulin levels is one of the risk factors, so is IGF-1, an insulin-like growth factor. The aromatase enzyme in fatty tissue turns male type hormones into estrogen, which also can stimulate cancer growth.

Carbohydrate restriction diet to prevent obesity

Low carb diets like the Mediterranean diet, the ketogenic diet and the Atkins diet will drop blood insulin and lactate levels. Cancer size and cancer growth are related to insulin and lactate levels. A low carb diet can reduce insulin-mediated uptake of sugar into cancer cells.

Research has shown that cancer metabolism slows down when a 10%-20% carb/high protein diet is consumed by the patient. This reduces the amount of sugar that is taken up by cancer cells. It also reduces insulin, so there is less cancer growth. A ketogenic diet is a more strict way to restrict carbohydrates. Intermittent fasting is also a useful method to reduce carbohydrate intake.

Here is an interesting study that illustrates the power of intermittent fasting. The study involved 2413 patients with early breast cancer who were followed for 7 years. Those breast cancer patients, who consistently did not eat anything between dinner and breakfast for 13 hours or more, had a 36% lower risk of having a cancer recurrence. There was also a 21% lower risk of dying from breast cancer when fasting was done for 13 hours or more overnight.

Supplements to prevent obesity, diabetes and cancer

A low carb diet and in some cases even a ketogenic diet is beneficial as a baseline. A regular exercise program is also useful for general fitness building and cardiovascular strengthening. In addition Dr. Chilkov recommended the following supplements.

  1. To reduce inflammation in the body, Dr. Chilkov recommended taking 2000 to 6000 mg of omega-3 fatty acids per day (molecularly distilled fish oil).
  2. Berberine 500 to 1000 mg three times daily. Dr. Chilkov said that Berberine has anti-cancer properties, improves insulin sensitivity and reduces absorption of sugars in the intestinal tract.
  3. Curcumin inhibits cancer cell division, invasion and metastatic spread through interaction with multiple cell signalling proteins. Several researchers showed that curcumin could lower blood sugar levels by stimulating insulin production from beta cells in the pancreas. Triglycerides, leptins and inflammation in fat cells are also lowered by curcumin. Insulin sensitivity increases through the action of curcumin. Dr. Chilkov recommended 300 mg/day of curcumin for 3 months.
  4. Resveratrol, the bioflavonoid from red wine is a powerful anti-inflammatory. This antioxidant has several other effects, which make it challenging to measure each effect by itself. This group of investigators managed to simultaneously measure these effects. They found that resveratrol lowered the C-reactive protein by 26% and tumor necrosis factor-alpha by 19.8%. Resveratrol also decreased fasting blood sugar and insulin; in addition it reduced hemoglobin A1C and insulin resistance. The recommended daily dose of resveratrol is 1000 to 5000 mg.
  5. Green tea catechins (EGCG) help to normalize the glucose and insulin metabolism. The dosage recommended was 1-3 grams per day.
  6. Reishi mushroom (Ganoderma lucidum) contain polysaccharides with antidiabetic and antiobesity effects. They make gut bacteria produce three types of short-chain fatty acids that control body weight and insulin sensitivity.
Obesity And Diabetes Can Cause Cancer

Obesity And Diabetes Can Cause Cancer

Conclusion

Obesity is a risk factor not only for diabetes, but also for cancer. Chronically elevated blood sugars, increased fasting insulin levels and increased IGF1 levels can cause cancer. In addition they can stimulate tumor growth and increase cancer mortality. It is for this reason that the health care provider should screen all diabetics for cancer. In her talk Dr. Nalini Chilkov gave clear guidelines what supplements will be beneficial to reduce the risk of obesity and diabetes as well as cancer. Start with a healthy, balanced diet. Add an exercise program. Then consider some of the above-mentioned supplements to reduce your risk for cancer, diabetes and obesity.