Can a Low-Carbohydrate Diet Prevent or Treat Cancer?
Several lines of evidence point to the idea that restricting dietary carbohydrates may have beneficial effects in the prevention or treatment of cancer.
Scientists often grow human or animal cells in lab dishes in order to study their reactions to various stimuli, such as nutrients or drugs. Cell cultures give us reliable information on how cells work, and their relative cheapness and short time frame of experiments make them a great resource, but since they don’t represent a whole organism animal or human, results must be cautiously interpreted.
This makes sense due to the Warburg effect, which was discovered nearly 100 years ago by Otto Warburg. Cancer cells preferentially use glucose for energy in a process called anaerobic glycolysis. The PET scan, used to detect cancer, makes use of this effect by looking at tissues with increased glucose uptake, thus detecting cancer.
Curiously, Warburg’s original hypothesis that aerobic glycolysis itself could be the “origin of cancer cells” had not been proven directly. Our findings provide a hitherto-undescribed direct role of increased aerobic glycolysis in inducing the cancer phenotype, in which increased glycolytic activity regulates the canonical oncogenic pathways dynamically and reciprocally. These results may provide additional evidence for how hyperglycemia in diseases such as obesity and diabetes could provide a microenvironment that results in higher risk of some cancers. Additionally, our findings may explain how small molecules, such as metformin (used for treatment of diabetes and known to lower blood glucose levels), decrease the risk and mortality of several types of cancers.
Cancer has consistently been reported as rare to non-existent in peoples living in accordance with their traditional lifestyles, including Africans, American Indians, and Eskimos. Modern hunter-gatherer peoples eat far fewer carbohydrates, from 20 to 40% of calories, than do modern Americans, who eat 50% of calories as carbohydrates, on average. Hunter-gatherers also don’t eat highly processed carbohydrates, such as flour and sugar, which have been suggested to be uniquely involved in promoting cancer.
Thus, there are several reasons to think that a diet high in refined carbohydrates and/or sugar could promote cancer in humans.
Do low-carbohydrate (ketogenic) diets benefit cancer patients? This topic has engendered lots of controversy, with one side claiming that they could work wonders, the other side claiming a lack of solid evidence.
The majority of animal studies (72%) yielded evidence for an anti-tumor effect of KDs. Evidential support for such effects in humans was weak and limited to individual cases, but a probabilistic argument shows that the available data strengthen the belief in the anti-tumor effect hypothesis at least for some individuals. Evidence for pro-tumor effects was lacking completely.
Good evidence in animal studies, weak evidence in humans, and no evidence of a pro-cancer effect.
Conclusion: A good case, but more evidence needed
If the reports of low to non-existent cancer among peoples living a traditional lifestyle without Western foods holds true, then that gives us reason to believe in the refined carbohydrate and cancer hypothesis. (I say “if”, because many of the reports are older and non-systematic, but still a phenomenon remarked upon by many doctors who lived among these peoples.)
Animal studies are another brick in the evidence wall, but of course rodents aren’t humans.
The fact that cancer cells feed on glucose, and that insulin promotes cancer growth, lead to the belief that cutting dietary carbohydrates can only help prevent or treat cancer. Certainly, there’s no evidence that cutting carbohydrates is harmful in that respect – or indeed, in any other respect.
PS: For more on how to live longer and healthier with strength training, and avoid cancer the same way, see my book, Muscle Up.
Chelation therapy has been used to treat heart disease, and a randomized, placebo-controlled trial of chelation therapy showed that it works, which I wrote about in Heavy Metals and Heart Attacks. Further analysis of the results from the chelation trial have shown another interesting result: in patients who do not take statins, multivitamins prevent heart attacks.
The TACT Trial
Chelation therapy, the process in which doctors infuse EDTA into a patient with the aim of removing metals, has been practiced for decades mainly by alternative practitioners. The Trial to Assess Chelation Therapy, or TACT, was designed to rigorously test this therapy, and was originally thought of as a debunking study that would finally put the idea of chelation therapy to rest and confirm the mainstream proclamations of its uselessness. Unfortunately, or fortunately, depending on which side of health care you stand on, the trial found that, contrary to expectations, it worked.
Most of the patients in the trial, 73% of them, were taking statins, since these drugs are considered standard of care for heart attack patients. But 27% were not on statins, and this group was analyzed separately.
The group taking vitamins, as opposed to placebo, had 54% fewer events, a composite of cardiovascular mortality, stroke, or heart attack. See event rate chart below.
The researchers were flabbergasted:
“These findings were unexpected and have to be viewed with appropriate skepticism… The TACT investigators did not expect the OMVM regimen to produce clinically important benefits independent of the chelation treatment. The findings reported here were serendipitously discovered. The relative treatment effect seems quite large and this, in the presence of substantial noncompliance and what we think we already know about OMVM, makes these results seem implausible. However, implausible does not mean wrong. Under these circumstances, it is prudent to view these results skeptically and await TACT2 replication before any serious consideration is given to the potential clinical value of these findings.”
The MVM supplement
Previous trials have found no benefit of vitamins in cardiovascular disease, but most of them used either single vitamins or different formulations with much smaller amounts of vitamins and minerals.
In the study discussed here, the only reason they used vitamins is because chelation practitioners told them that they should, because that has been their practice. The ingredients of the MVM supplement can be found here. What jumps out are much higher amounts than in the Physician’s Health Study, as well as high amounts of vitamin A, C, B vitamins, and a hefty 500 mg of magnesium. Lots of other vitamins and minerals too.
In addition, the infusion used for chelation contained EDTA – based on kidney function, with a maximum of 3 grams – and 2 grams of magnesium chloride, 7 grams of vitamin C, potassium, and three B vitamins.
My bet is on magnesium as the main component of the supplement that lowered the risk of cardiovascular events.
Huge numbers of people do not get enough magnesium, as much as 50% of the population, and that figure is using the official RDA. At a more realistic intake of magnesium, many more are deficient. And magnesium deficiency is not readily detectable with standard lab testing. Magnesium deficiency can lead to hypertension and atherosclerosis.
Many magnesium supplements aren’t absorbed well. While the study doesn’t specify what type of magnesium the MVM contained, the fact that the patients got an infusion of 2 grams of magnesium chloride weekly guarantees that body magnesium levels increased.
Magnesium citrate is the best absorbed form of magnesium. I take this one. Don’t even bother with magnesium oxide, the kind found on drugstore shelves, as the body can absorb next to none of it.
Of course other vitamins and minerals may have contributed to the lower incidence of cardiovascular events. Maybe most of them together synergized. Of note, the supplement contained no iron.
Of interest, patients taking statins got no benefit from the vitamin/mineral supplement. That could mean a couple of things.
Statins cancel the benefits of vitamins and minerals on cardiovascular disease risk, or
Statins confer the same benefits as vitamins and minerals, and the addition of vitamins and minerals conferred no extra benefit.
By eyeballing the charts, my bet is on the first option: statins negate the benefits of vitamins and minerals.
What can we conclude, or at least conjecture, about these results?
For starters, it’s important to be well-nourished, as that can prevent or treat heart disease.
Multivitamins and minerals in supplement form may treat CVD.
Many people with cardiovascular disease may be malnourished – in fact, that’s a certainty in my opinion.
Emerging evidence indicates that vitamin K2 plays a large role in the prevention of heart disease and cancer, as well as other conditions. Vitamin K2 is likely one of the vitamins that people are most deficient in – the other being vitamin D – and therefore it may be worthwhile to supplement with it: vitamin K2, heart disease, and cancer.
Vitamin K2 – what it is
Vitamin K refers to a group of fat-soluble vitamins, K1 and K2. Somewhat confusingly, there are several different forms of K2 as well.
Vitamin K1, or phylloquinone, is found in plant foods, mainly green leafy vegetables. K2, or menaquinone, is found in animal foods, mainly dairy.
The relative risk of death from coronary artery disease in the highest tertile (third) of vitamin K2 intake was nearly 60% lower than those in the lowest tertile. I’ll take that degree of risk reduction any day of the week.
Risk of all-cause mortality was ~25% less, and the risk of aortic calcification was only about half that of the lowest intake group.
Of importance, intake of phylloquinones, or vitamin K1, was not associated with any of these outcomes.
These studies of course show associations and not causation, but there are good reasons to believe that causation is involved.
Vitamin K2 is involved in calcium metabolism; therefore reduced calcification of arteries by vitamin K2 is likely to be causal.
Since vitamin K2 comes mainly from animal foods, a healthy user effect might be ruled out. People conscientious of their health have reduced their consumption of animal foods over the past several decades, following mainstream advice.
The inverse association between vitamin K2 consumption and lower rates of heart disease makes sense, since one of the functions of vitamin K2 is in calcium metabolism. Calcification of the arteries is a cause of coronary heart disease. Essentially, vitamin K2 gets calcium into the right places, bones instead of arteries.
Given the above evidence – and there’s a lot more – I want to be sure I get adequate vitamin K2.
If you supplement with vitamin D – which I do – you should also be sure to get adequate K2; both are important for calcium homeostasis, so you shouldn’t get one without the other.
Pasture-raised meat and dairy are the best sources of vitamin K2. However, they’re expensive, most people never eat them, and I only seldom do. Feedlot meat and dairy doesn’t have much. Kerrygold butter from Ireland, sold here in the U.S., is a good source, although amounts of K2 also appear to be dependent on the season of the year, so you can’t be sure.
Given all of this, I supplement with K2. It’s the only vitamin I take besides D. Heart disease runs in my family, and I don’t feel like getting it.
I’ve been supplementing with a form of K2 known as MK-4, but I recently switched to the MK7 form. Here’s why:
The study compared the administration of MK-7 to that of MK-4, and found that “MK-7 was well absorbed and reached maximal serum level at 6 h after intake and was detected up to 48 h after intake. MK-4 was not detectable in the serum of all subjects at any time point..”
We conclude that MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels. MK-7, however significantly increases serum MK-7 levels and therefore may be of particular importance for extrahepatic tissues.
I immediately bought an MK7 form of vitamin K2. There are many brands and sizes, and this one seems to be the best value.
Vitamin K is important to the health of your arteries. Atherosclerosis is one of the leading causes of death in the developed world.
Therefore, I take a vitamin K supplement. The MK7 form is the one to get.
Carbohydrates Inhibit Insulin Sensitivity from Exercise
Exercise increases insulin sensitivity, and that’s one of the best reasons for doing regular exercise. But carbohydrates inhibit insulin sensitivity from exercise, so if you eat carbohydrates after exercise, you could be sabotaging your exercise and not getting all of its benefits.
Insulin sensitivity is critical for health. Most if not all of the diseases of civilization – heart disease, cancer, diabetes, Alzheimer’s, and the rest – are accompanied by insulin resistance, that is, a decrease in insulin sensitivity. Increasing insulin sensitivity could help prevent most of these diseases.
The chart below shows what happens when a group of men and women have their insulin sensitivity/resistance measured and are followed for approximately 5 years. They were grouped into tertiles (thirds), equal-numbered groups according to insulin resistance. The group with the greatest insulin sensitivity (lowest resistance) had zero cases of heart disease, stroke, cancer, hypertension, or type 2 diabetes. The majority of cases were in the group with the highest insulin resistance. (Details here.)
Maintaining good insulin sensitivity is that important – your life could depend on it.
But eating carbohydrates may sabotage the ability of exercise to increase insulin sensitivity.
The effect of carbohydrates after exercise
Exercise uses a combination of the two kinds of stored energy in the body: carbohydrates, and fats. Generally, the higher the exercise intensity, the greater the amount of glycogen, the storage form of carbohydrate, that the body uses. Low intensity exercise uses a greater amount of fat. The ratio of carbohydrate to fat burned can be determined using the respiratory quotient, a test done in the physiology laboratory.
Even a relatively lean person has enough calories stored as body fat to last for weeks or perhaps even months without eating. Using myself as an example, at 160 pounds body weight and 12% body fat, I have 19 pounds of body fat. At 3,500 calories per pound of body fat, and at a 2,000 calorie daily requirement, my fat stores might last over a month without eating.
The ability of exercise to drain glycogen stores is crucial to its ability to improve insulin action. If you immediately replace the lost glycogen by eating a high-carbohydrate meal, you may lose the insulin-sensitizing benefit of exercise.
Fourteen healthy adults exercised for 90 minutes at 70% VO2max. They then drank either a placebo, or a drink with about 220 grams of carbohydrate in the form of maltodextrin. The study had a crossover design, so all participants did both interventions. They then went through a glucose tolerance test the next day, and glucose and insulin were measured. Results below:
Both glucose and insulin were higher in the group that replenished glycogen stores with maltodextrin.
Furthermore, during the glucose tolerance test, those who had taken the carbohydrate burned less fat.
The present study demonstrates that replacement of the carbohydrate utilized during a single bout of exercise impairs both insulin sensitivity and glucose tolerance by ~20–25% the following morning, relative to when the exercise-induced carbohydrate deficit is maintained. Importantly, these changes were most clearly apparent in the postprandial state. Furthermore, postprandial fat oxidation was suppressed by post-exercise replacement of carbohydrate use.
Previous work has demonstrated that, whilst exercise is a potent method of stimulating muscle glucose uptake and insulin sensitivity, the carbohydrate deficit induced by exercise is key factor that mediates these responses.
The insulin-sensitizing effect of exercise depends in part on depleting glycogen stores. Replacing glycogen with a large amount of carbohydrate, as is the practice for many, both athletes and non-athletes, impairs the effect of exercise.
Don’t self-sabotage your exercise regimen by eating lots of carbs.
Since the higher the exercise intensity, the more glycogen is burned, high-intensity exercise is a good way to improve insulin sensitivity.
PS: For more on high-intensity training, see my book, Muscle Up.
Many people are under the impression that you just can’t get enough exercise. A healthy activity must be healthier if you get more of it – right? Well, not necessarily; it’s possible to get too much exercise.
Exercise isn’t natural
“Physical activity” is the term of art used in science for any movement of the body using skeletal muscles that leads to energy expenditure. Basically, almost anything other than sleeping or sitting in a chair involves physical activity, some of it strenuous – working a construction job, for instance – some of it much less strenuous – working an office job, or walking the dog.
Exercise is meant to improve physical fitness and health. To improve fitness, one must place a stress on the body, so that it responds to the stress by getting stronger and more resistant to injury, or by increasing cardiovascular capacity (VO2max) so that it can perform better the next time the stress is encountered.
Exercise is hormesis, or the process by which a low-dose stress or toxin improves health. But as with any stress, it can be overdone. Below is a chart for the incidence of atrial fibrillation in people who exercise (see previous link for details).
Those who exercised at high volume (not intensity as I explain in the previous article) had a higher incidence than those who exercised at moderate volume. It’s clearly possible to exercise too much.
Do non-human animals exercise? Some of them do seem to run around for no purpose other than the running, or perhaps enjoyment.
It’s possible that animals, including humans, have some kind of built-in need for exercise so that they can maintain their health. The cult of athletics goes back at least as far as ancient Greece, and in primitive societies, dancing and simulated fighting are common.
But, if there’s a built-in need for exercise, there’s also a built-in “exerstat” that tells an animal when to stop, when to rest. Animals rest when needed, and human hunter-gatherer societies are well-known for taking it easy when necessary.
We modern humans are capable of overriding our “exerstat”.
What happens when you override your exerstat? You feel rotten: tired, weak, and with a depressed mood.
Yet many people with these symptoms continue to exercise more than they should.
These people don’t understand that exercise is a stress, and requires proper rest and recovery.
In the video below, Doug McGuff, M.D. (“Body by Science“) discusses how his 3 times a week workout regimen made him feel like “crap”. He advocates a once-weekly workout now.
Exercise forces adaptive changes on the body. Like a drug, exercise requires a minimal effective dose. Just as giving more of a drug doesn’t always mean better results, more exercise doesn’t necessarily improve health either.
The multi-billion dollar fitness industry wants you exercising constantly, since there’s more money in it for them.
The health-conscious man often looks at the average person, who exercises little if at all, and says to himself, “I’m not going to be like that.” But he then goes overboard and exercises too much, doesn’t feel well, and wonders why.
It took me years of trial and error to discover my optimal frequency of exercise, which is currently two 35-minute sessions a week of high-intensity lifting. Sometimes even that feels like a lot. Before I cut back, I often had the same experience as McGuff: I felt terrible and had days where I didn’t feel like I was capable of doing much of anything.
If you do any sort of exercise of a higher intensity than, say, walking, your body needs rest and recovery. If the exercise isn’t too intense, you might only need a day. But if you lift weights, you need more time for rest and recovery.
Realize that exercise is a stress and it isn’t necessarily the case that more is better.
Besides improving health, the purpose of exercise is to make you feel better, with higher energy and a better mood. If exercise isn’t doing that, your dose may be too high, and you should cut back.
PS: For the best exercise, see my book, Muscle Up.
Alan S. Green, M.D.: The most vulnerable medical group today are the 20 million Americans in the 40-70 age group who are APOE4 carriers. They are at high risk of Alzheimer’s disease.
Since 2010, there have been studies with excellent mouse models of AD with human genes for AD showing rapamycin will prevent AD. The most important study was a 2015 study in which mice were given human genes for APOE4.
It seems like the attitude in clinical medicine is what happens in the research laboratory stays in the research laboratory, at least as far as generic drugs like rapamycin are concerned.
Many people are having genetic testing and finding out they are APOE4 carriers. The APOE4 community need three things. (a) The need convenient access to the best current scientific information. (b) They should be able to see a physician who’s main interest is providing the best prevention plan and (c) they need access to what looks like, in the basic science laboratory, the most effective medicine in preventing AD in APOE4 carriers, even if that use is “0ff-label”.
PDM: Can you briefly summarize your website?
ASG: The website provides a current understanding of the etiology and development of AD in APOE4 carriers. The websites highlights all the basic research and mouse studies showing rapamycin will prevent AD in APOE4 carriers. The website discusses risk and lifestyle required to lower that risk. It lets people looking for help know there is a medical office with the primary interest of prevention of AD in APOE4 carriers, using all the tools currently available, even if medication is “off-label”.
PDM: You are offering rapamycin “off-label” prior to human clinical trials proving that rapamycin prevents AD in humans in APOE4 carriers; when do you think traditional medicine will have results from human clinical trials showing rapamycin is effective to prevent AD?
ASG: My opinion is that is at least 10 years down the road. The problem with that is many APOE4 carriers don’t have 10 years to wait. Even if rapamycin works in early stage to prevent AD; it will not work in late stages. Prevention is absolutely required because chance of cure of established AD is extremely remote possibility.
PDM: How will you know if the treatment is working?
The best test is PET scans to study any changes in cerebral blood flow.
However, we can also follow progress with psychological testing to see small impairment or improvement in memory. Decline in memory is a very sensitive early indicator of cognitive decline.
PDM: With the current interest in prevention of AD, why has progress with rapamycin been so slow ?
Rapamycin is a generic drug. There is no pot of gold at end of the rainbow for rapamycin.
PDM: Since our last interview in May 2017, how have you been doing? Do you still feel that rapamycin has been crucially important in your return to health?
ASG: I will turn 75 this February and have now been on weekly rapamycin for 2 years. I have not had any significant side-effects from weekly rapamycin. As regards aging, I feel like I am now in “remission”. I am very happy about the function of my brain and heart. I credit Mikhail Blagosklonny and rapamycin for giving me a new lease of life. I consider rapamycin the most important new drug since discovery of penicillin 90 years ago. [Emphasis added – PDM]. The failure of the medical community to have widespread use of rapamycin to prevent age-related diseases including AD is an enormous loss to older people.
PDM: How is your rapamycin-based practice for prevention of age-related diseases going ?
ASG: For the past eight months, I have treated a fairly small number of patients. The remarkable thing is that average distance from where patients live to my office is probably around 1000 miles. I have seen patients from UK, Canada, Cayman Islands, and about 20 states including California, Texas, Florida, Massachusetts. Most patients fly to NYC. They are a remarkably knowledgeable group.
Weekly rapamycin is very well tolerated and only a few patients have had any side-effects.
PDM: As a physician in the anti-aging field, what do you consider the most important development is for 2017?
ASG: Matt Kaeberlein’s experiment with old companion dogs. He gave old dogs intermittent rapamycin for 3 months and showed improvement in cardiac function. Some of the dog owners said their old dogs were running around like puppies.
[This short video shows the remarkable results of a dog on rapamycin – PDM]
However, in my opinion, for the most part, the anti-aging field is dominated by quack medicine and junk science.
PDM: How can people discern real science and results in treating aging?
ASG: Mikhail Blagosklonny said aging and age related disease were connected like smoke and fire. This means an anti-aging drug should both extend the lifespan of all different organisms tested including yeast, flies, worms, and mice; but should also prevent almost all age-related disease including cancer and heart disease.
PDM: How big an effect do you think rapamycin will have on human lifespan ?
Rapamycin has one effect, it decreases mTOR. Elevated mTOR appears to play a very major role in age-related disease. I expect rapamycin will have a huge effect on preventing age-related disease and keeping people healthy in their seventies and eighties. Other than that, we will have to wait another 20 or 30 years to see the full impact of lowering mTOR.
PDM: Getting back to your new website, what should APOE4 carriers know?
ASG: First they need to understand their real risk and the things they should do to lower their risk.
Everybody knows APOE4 carriers are at increased risk; but the increased risk is greatly minimized by how the numbers are presented. Overall APOE4 carriers have a 3.2 fold increased risk; but their mean age of onset is 10 years sooner than non-E4 carriers. In the 60-69 age group, they have a 5.6 fold increased risk, in the 70-79 year age group a 4 fold increased risk. The increased risk is only 1.7 fold in the 80-89 age group. When averaged together the large number of cases of AD in 85 plus age group who are non-E4 carriers with the AD cases in E4 carriers in the younger age group, it creates a false impression. It is not that the lifetime risk in non-E4 group is 9% and lifetime risk in E4 group is 29%, it is the 10 years sooner mean age of onset that makes the huge difference in impact.
The impact of lifestyle on APOE4 carriers is very large; in contrast, lifestyle seems to have a small impact in non-E4 carriers as regards risk of AD. Any statement about lifestyle as regards risk of AD in general population is worthless and dangerously misleading as regards APOE4 carriers.
There are very many dramatic examples of this: High saturated fat diet increases risk of E4 carriers 11 fold; but has no significant increased risk for non-E4 carriers. Frequent alcohol intake increases risk 7 fold vs never drinkers in E4 group; but actually lowers risk in non-E4. Overweight, obesity, diabetes greatly increase risk in E4 carriers compared to non-E4 carriers. The benefits of physical activity is much greater in E4 group. A sedentary lifestyle with overeating, eating large amount of red meat, overweight combined with moderate alcohol intake might be reasonably safe for non-E4 carriers; but very high risk for APOE4 carriers. Information reported might be correct for non-E4 carriers; but very different for E4 Carriers. Therefore, E4 carriers they must know their E4 status so they can take appropriate steps to minimize their risk.
PDM: What basic science should they know?
The website deals with this in two sections; Basic Science and Mouse studies.
AD in APOE4 carriers is a 2 hit disease. (Zlokovic theory) The first hit is deterioration of the vascular system. The 1st hit develops decades before the second hit and decades before first onset of cognitive changes. PET scans of cerebral blood flow shows deterioration starts in the 20-39 year age group in E4 carriers. The damage to cerebral blood flow results in accumulation of amyloid. The accumulation of amyloid then triggers the second hit which has been called the amyloid cascade. The second hit includes accumulation of hyperphosphorylated TAU, which is extremely damaging to nerve cells. The accumulation of amyloid is first noted age at mean age 56 in E4 carriers, compared to age 76 in non-E4 carriers.
The 2 hit theory, shows that deterioration of vascular system precedes hit 2 and amyloid cascade by decades. This provides excellent opportunity to prevent deterioration of vascular system in E4 carriers.
APOE4 is not a mere risk factor; but rather the cause. The specific etiology on a molecular level is that in APOE4 carriers the ApoE4 lipoprotein fails to combine with transport protein LRP1. [weak ligand] This results in activation of proinflammatory substance CypA which then activates the usual suspect NF-kB which activates MMP9 which then breaks down BBB (blood-brain barrier). The important thing to understand is that there is a specific pathway and rapamycin blocks this pathway which prevents damage to BBB and cerebral blood flow.
The Mouse studies section looks at 8 mouse studies with transgenic mice with human genes for AD. The most important study was a 2015 study in which mice were given human APOE4 genes. [Spoiler alert]. In every study rapamycin prevents development of AD like pathology and cognitive deficits.
The basic science details very many precise steps in two hit development in which rapamycin lowers mTOR and blocks the various steps.
Examination of the human brain from APOE4 carriers with AD, shows these same finding in the mice who were given human APOE4 genes are also present in the human brain.
PDM: What do we know about human APOE4 carriers that suggests rapamycin will prevent development of AD in this group?
ASG: Everything that raises mTOR in human APOE4 carriers, very much increases risk of development of AD. High calorie diet, overweight, obesity, diabetes all increase mTOR and all very much increase risk of development AD. Things like exercise and low calorie diet which reduce mTOR, lower risk of AD.
PDM: What methods are some APOE4 carriers now using to decrease their risk?
ASG: Many of them are using a regime that includes fasting, avoiding sugar and red meat. These are all methods to lower mTOR.
PDM: Would you expect rapamycin to protect against AD in non-E4 carriers?
ASG: Yes. Rapamycin would be expected to protect against AD in non-E4 carriers by the following mechanism:
Rapamycin protects against hyperphosphorylation of Tau by many mechanisms as discussed in the Tau section. Tau is major player in AD.
Rapamycin would prevent accumulation of amyloid by increase in autophagy.
Increase in amyloid causes increases in mTOR which increases Tau, rapamycin blocks this step.
Rapamycin would help preserve cerebral blood flow by decrease in CypA[Symbol]NF-kB[Symbol]MMP9 pathway leading to breakdown of BBB which develops in old age due to very marked age-related decrease in LRP1.
Rapamycin increases cerebral blood flow by increased nitric oxide.
The mean age of AD in non-E4 carriers is 85. Starting rapamycin at age 75 should be helpful to prevent AD in non-E4 carriers. This is in contrast to E4 carriers who, in my opinion, should probably start rapamycin at age 45 to prevent deterioration BBB and cerebral blood flow.
PDM: What is the effect of rapamycin on the normal aging brain?
Based upon mouse studies rapamycin might prevent memory decline. Age 60 is probably a good age to start to protect the brain from age-related memory decline.
Rapamycin increases catecholamines in the mid-brain which may prevent against age-related depression.
PDM: Many people have asked me whether rapamycin might impair muscle anabolism (growth) in resistance training. What do you think?
ASG: It might. mTOR builds large muscles.
However, rapamycin would help prevent against sarcopenia (muscle wasting in aged) by decreasing inflammation.
Rapamycin may also help preserve muscle strength by an increase in number of mitochondria by preserving mitophagy.
[See below for more on this. – PDM]
PDM: What effect would you expect of rapamycin on testosterone and sexual performance ?
ASG: Intermittent rapamycin would not affect testosterone levels in contrast high levels daily Rapamycin.
Rapamycin causes an increase of catecholamines in midbrain which might increase sexual interest.
Rapamycin increase in activity of NOS (nitric oxide synthase) and increase in nitric oxide could improve sexual performance.
PDM: Insulin resistance is an important cause of pathology in the diseases of civilization; what’s the relation of insulin resistance to AD?
ASG: You are correct. Major cause of civilization-related disease is through insulin resistance / high insulin / high mTOR pathway. Insulin resistance causes high insulin levels and high mTOR. High mTOR is then the major driving factor in most age-related disease and AD.
Insulin resistance should be viewed as a very serious disease with diabetes just one of the complications of insulin resistance.
Addendum: Rapamycin and muscle
Dr. Green above noted several effects of rapamycin on muscle, some of them opposing each other, so here’s some more information.
Rapamycin-treated mice had endurance equivalent to that of untreated controls, and isolated, permeabilized muscle fibers displayed similar rates of oxygen consumption. We conclude that the doses of rapamycin required to extend life do not cause overt mitochondrial dysfunction in skeletal muscle.
Here we show that rapamycin treatment blocks the early (1–2 h) acute contraction-induced increase (∼40%) in human muscle protein synthesis. In addition, several downstream components of the mTORC1 signalling pathway were also blunted or blocked by rapamycin.
Comment: The subjects in this study took a huge dose of rapamycin, 12 mg, immediately before a workout. Below is concentration of rapamycin in blood by time.
Insulin response was blunted during and after exercise compared to controls, and muscle protein fractional synthetic rate in rapamycin treatment was also blunted.
The type of rapamycin treatment that Dr. Green advocates and prescribes is once weekly and at a much smaller dose. An otherwise healthy man aged about 60 might take 2 mg rapamycin weekly, only 1/6 the amount in the above experiment that blunted muscle synthesis following resistance training.
Here’s a case where timing would be very important. Someone could take rapamycin but do strength training away from the dose, perhaps more than 2 days later. As I understand it, the type of mTOR activation that promotes aging is chronic activation. An analogy is with insulin activity: at times you want insulin to increase and spike to high levels, such as after a meal, but it’s deleterious to health for insulin to be constantly elevated (hyperinsulinemia), as it leads to insulin resistance. With mTOR, spikes in its activity should be fine; chronic, low-level activation of mTOR is what leads to aging. That’s my speculation and I don’t want to speak for Dr. Green.
Update: A commenter below remarks: “As a patient of Dr. Green I appreciate the spread of information. I currently take 2 mgs of Rapamycin every 2 weeks and have noticed ZERO negative effects on my weight training and strength. BTW – I’m 63 and will be 64 in July.” That’s the sort of information we need but which is necessarily in short supply at this time. Likely we’ll know a lot more about the interplay between rapamycin and muscle in 10 years time, when many more people will have been taking it. Meanwhile, the comment lends some support to my hypothesis that low, non-daily doses of rapamycin do not compromise muscle growth and/or resistance training.
Why are so many people so overweight or obese? Why are so many people trying, unsuccessfully, to lose weight? If you can answer those questions correctly, then you can lose weight and then stay lean and trim. Read on for how to lose weight, really.
Two big mistakes in weight loss
The two biggest mistakes in weight loss are:
Calories in, calories out determines weight loss.
You can exercise body fat away.
Calories in, calories out
On the most basic level, this statement has some truth. If you don’t expend more calories than you take in, you won’t lose fat.
But that’s like saying your house burned down because it was ignited. Ignition is a necessary condition of your house burning down; the question is how to prevent your house from being ignited. It confuses an ultimate cause with a proximal cause.
In weight loss, the question is how to expend more calories than you take in.
Voluntary reduction of calories, aka a “reducing diet”, has been repeatedly shown to fail. Doctors commonly tell their patients to eat less. If that worked, no one would be overweight.
Hormones control the amount of fat that you carry on your body. Insulin, leptin, and adiponectin regulate body fat, and even your gut microbes play a role; two ways they do this is by regulating hunger, and regulating metabolism.
If you voluntarily reduce your calorie intake, you get hungry, and/or your metabolism declines. You then either eat more because you’re hungry, or expend less energy because your metabolism declined. Either way, you’re still taking in more calories than you expend.
Hunger always wins in the end, as few people can withstand it. Or even if you can, your metabolism – the rate at which you burn calories – declines, and weight loss stops. Hormones do this.
The key is to reduce hunger, so that you easily reduce the amount of calories that you consume.
Processed foods contain refined carbohydrates (flour mainly), sugar, and seed (vegetable) oils, all of which interfere with your body’s weight-regulating mechanism. Don’t eat fast food or junk food, ever. The best policy is to eat nothing that comes in a box or bag or that has seen the inside of a factory or fast-food restaurant.
Eat whole, unprocessed foods, like meat, fish eggs, vegetables, maybe a little fruit (careful, fruit contains sugar), cheese. Prepare your own meals.
Exercise is another way you can allegedly increase caloric balance in your favor. But that doesn’t work too well either. The reason is the same as for voluntarily reducing calories: exercise makes you hungry.
But exercise is just not very effective for weight loss.
When you exercise, you get hungry, and it’s almost trivially easy to consume more calories than you burned during exercise. Not only that, exercise doesn’t even burn that many calories. Treating yourself at Starbucks after the gym, or even eating a protein bar, will negate any progress in calorie-burning you made.
Big Food wants you ignorant and to blame yourself
It’s very common to see overweight people in the gym or the park trying to exercise away their excess fat, and judging by their results, it’s not working. Going from what I see others eat, I’m sure they’re not making sustainable dietary changes.
Unfortunately, most people believe that exercise is the key to weight loss. Why is that?
By promoting the idea that exercise is the key to weight loss, they take away the blame from their junk foods and put the blame on you. If you can’t lose weight, they say, you’re not trying hard enough, or you’re just lazy.
The fitness industry isn’t innocent here either. Gyms, fitness magazines, and trainers perpetuate the notion that you need lots of exercise to lose weight. They can sell more of their products and services to overweight people by promoting the idea that you need them to lose weight.
To actually lose the fat, avoid all processed foods, which contain large amounts of refined grains, sugar, and seed oils. Cut your carbohydrate intake.
Weight loss on an unrestricted low-carbohydrate diet vs a calorie-restricted low-fat diet. Yancy, William S., et al. “A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: A randomized, controlled trial.” Annals of Internal Medicine 140.10 (2004): 769-777.
Note the above chart, which shows far better results for a low-carbohydrate diet, which was unrestricted in calories.
One of the great benefits of eating low-carbohydrate whole, unprocessed foods is that it reduces your hunger. In trials of low-carbohydrate diets, one thing that’s been seen again and again is that people spontaneously reduce their caloric intake on this diet. That’s one of the keys to the success of this diet right there.
In my book, Muscle Up, I wrote extensively on how strength training, aka weightlifting or resistance training, is one of the most important things you can do to be healthy and prevent aging. Getting people to take up weight training was my main motivation for writing the book, since unfortunately hardly anyone does it. One reason (among many) they don’t do it is because they believe it’s difficult, results too hard to attain, or it takes a lot of time. Let’s explore that and see how you can build muscle at any age.
My results in one hour weekly training
Here’s a photo taken on 1/6/18 that I recently posted on Twitter. I’m 5’10”, 160 pounds, and am 62 years and 10 months old.
Here’s another photo taken two weeks later (in a new shirt).
I’ve been lifting weights for about 7.5 years now, although most of the muscle I put on was in my first year of training. I’ve been using a high-intensity style of training for under two years.
People ask me a lot about what I do to get this way, and while I’m proud of the way I look, I consider myself totally average physically. I’m not a talented athlete and have never played team sports, having spent most of my life reading. I merely train with consistency and have my diet dialed in.
I train a total of just over 1 hour a week, using 2 approximately 35-minute sessions. I emphasize this point because many people are under the impression that building muscle requires long hours in the gym, and it does not. However, there are a few keys to making 1 hour a week training work.
Work out with intensity. The gym isn’t for socializing or fooling around. Go into the gym with the intention of crushing your workout, then do so.
No rest between sets/exercises. Pause only to break down or set up equipment, or if need be, to catch your breath. Quickly move to the next set/exercise. This is great for cardiovascular conditioning too.
No looking at your phone. Or the TVs on the wall.
The fitness industry – magazines, gyms, trainers – have a vested interest in promoting the idea that you need to be in the gym constantly to be in shape. But you do not, if – and it’s a big if – you know what you’re doing.
The only “muscle-building” supplements I take are 25 grams of whey and 5 grams of creatine right after my workout. So, only twice a week. Even these may be superfluous but I use them as insurance since I don’t want to leave any gains on the table. (My whey of choice.)
Almost the only other exercise I do is walking a couple miles on off-gym days, and I do that consistently.
Diet is extremely important for both leanness and muscularity.
I eat what I’d describe as a low-carbohydrate paleo diet. At my meals, I emphasize meat or eggs, and eat one or the other at every meal. In my opinion, healthy diets should be based this way.
I also eat dairy: cheese, full-fat plain yogurt, and cream, but not milk, which contains lactose and reliably gives me acne. I also eat vegetables, mainly things like onions or mushrooms that go with meat, but I hardly eat any fruit. I drink coffee, tea, and wine, and the occasional cocktail.
With the exception of a rare cheat, I don’t consume grains, soy, seed oils, or sugar. Basically no processed food at all. No bread or pasta, no desserts (except occasional dark chocolate), no breakfast cereal or bagels, etc.
The important part about diet is to have it dialed in. I don’t have garbage food in my house, and rarely eat outside it. If I do, I make every effort to eat healthy.
Building muscle and staying lean is easy
Staying fit and lean and building muscle is easy.
The key is to have your routine ON LOCK.
If you have your diet down, don’t eat anything else. No cheating. Don’t have crap food in your house, and refuse to touch it outside it.
Gym sessions are twice a week, about 30 minutes at a time. Everyone has time for that. If you say you don’t, then cut back on TV or internet surfing. If your day is too busy, get up half an hour early twice a week and go to the gym in the early morning.
Being fit is a lifestyle. You can’t hope to “go on a diet”, lose some weight, and then return to your former ways. That’s a recipe for failure.
And, while any exercise is better than none, to be fit you need to exercise consistently. Not necessarily a lot, but you must do it regularly.
Following these simple rules can help build muscle at any age. If you’re getting older, you need never worry about weakness and frailty. If you’re younger, you’re building a solid foundation both for the present and for your older age.
When to Collect Social Security Depends on Your Life Expectancy
One of the decisions one must make as one ages is when to collect a pension, such as Social Security in the U.S. Since we’re all about anti-aging and lifespan here at Rogue Health and Fitness, I thought it would be of interest to look at this topic, since I’m faced with the choice soon and I’ve been looking into it. When to collect Social Security depends on your life expectancy. (Among other things.)
The U.S. has the Social Security system, and this discussion will be about that, since other countries may have systems with different rules.
With Social Security, the amount you get per month varies widely depending on when you begin to collect it, hence the importance of the decision as to when to start. The earlier you begin to collect, the smaller the amount of money you get per month.
The longer you live, the greater the total amount of money you collect, since benefits last until death. (In theory, although there’s a wrinkle to that as we’ll discuss.)
The earliest retirement age is 62, and a large number of people begin to collect at that age, about one third, and only 4% of people wait until they’re 70, the age at which benefits no longer increase. This tells me several things about this large number of Americans:
they dislike their jobs and can’t wait to retire
they work physically demanding jobs that they’re too old to do anymore
they’re broke and can’t wait any longer to start collecting
they’re in ill health and/or don’t expect to live very long
they have high time preference, i.e. less ability to delay gratification
they believe the Social Security system won’t last
some combination of the above.
The maximum Social Security benefit for a retirement at age 62 is $2153 per month, at full retirement age, $2687, and at age 70, $3538. That’s 64% more money per month for the highest retirement age vs the lowest.
The maximum benefit at age 70, if calculated using the current 10-year Treasury bond rate, is like getting the interest payments on a bond worth $1.8 million, or $1.18 million if using the current AAA corporate bond rate.
Full retirement age varies; formerly 65, it now depends on when you were born. For me, for example, it’s 66. Full retirement age is arbitrary however, since you can begin to collect your pension at any age between 62 and 70. There’s no point to waiting past 70, since you get no more money for doing so, and you can only lose money.
The question as to when to collect obviously revolves around many factors, including personal circumstances, but what we want to figure out here is how to collect the maximum amount in your lifetime. That depends on when you start to collect, and how long you’ll live.
I believe I’ll live past 80, so I should wait to collect, if maximizing my lifetime amount is my goal.
However, if you believe that having more money earlier in your life is better than having it later – and it is, according to both standard financial theory and human psychology – then that introduces yet another variable.
Or, maybe you don’t think the Social Security system will last, in which case the earlier you start collecting, the better. Maybe you have enough money even without Social Security, in which case it’s better to wait to collect.
As you can see, the decision as to when to collect Social Security is not easily made. If you do an internet search for this, you get answers that are all over the place.
Lifetime earnings are not the only factor to consider. However, I believe I’ll live at least into my 90s (knock on wood) and possibly longer. I believe I’ll be lifting weights in my 80s, and if I ever become frail due to age, it will be at an age much older than most people become frail.
As someone gets very old, medical expenses can be expected to be higher, and there might be a need for special care, so those are reasons why someone might want or need more money per month than when younger. On the other hand, an older person might not be spending much on other things, such as vacations or fancy cars.
Normally, it would always be a good thing to delay gratification in order to collect a higher amount of money. This is what anyone who invests their money does: by foregoing current spending, they invest their money in the hope of having a larger amount of money later.
But in the case of Social Security, we’re dealing literally with matters of life and death. Can you really or fully apply financial principles to your own life and death? Nevertheless, we’re forced to try.
Even with my belief that I’ll live at least into my 90s, that’s a long way away, and making the leap of imagining myself at that age is difficult. The uncertainty of life accelerates with aging. My default presumption is to wait until I start collecting, but the more I look into it, the less certain I am.
The standard answer to whether to wait past the age of 62 to collect Social Security depends on whether maximizing lifetime income is the goal.
That may not be the case for many people. Having the money to spend when (somewhat) younger may make more sense.
Ultimately, the decision is a highly individual one.
PS: To increase your lifetime Social Security income, follow the practices in my book, Stop the Clock.
PDE5 is upregulated from 2- to 5-fold in human heart disease. Inhibition of PDE5 with sildenafil (Viagra) protects against ischemia/reperfusion injury, which means it increases cellular antioxidant protection mechanisms.
Mikhail Blagosklonny, M.D., the noted scientist who studies aging, mentioned PDE5 inhibitors as part of a suggested, or testable, anti-aging drug combination, along with rapamycin, metformin, aspirin, ACE inhibitors, and beta blockers. He writes that they are remarkably safe and are already being used in the treatment of pulmonary hypertension.
Levels of the enzyme PDE5 appear to rise with age, and therefore inhibiting them can bring them to youthful levels, and prevent or help to treat diabetes, heart disease, and cancer.
PDE5 inhibitors increase the level of nitric oxide (NO), which is important for endothelial (vascular) function; that’s how they work to increase erectile function.
Why would they help decrease heart attacks in diabetics?
What I’m waiting for is a study that shows PDE5 inhibitors increase lifespan in normal laboratory animals. My guess is that this will happen – probably someone is already working on it. A drug that fights all of the main diseases or signs of aging, namely cancer, heart disease, diabetes, and cognitive decline, is one that fights aging itself, since aging is the underlying driver of all of these problems.
Another way to put it is that these drugs may not only increase median lifespan, which is what a drug that fights one disease does, but maximum lifespan, which is what a drug that fights aging does.
The PDE5 inhibitors have varying half-lives, which is the time it takes for half of the drug to be metabolized or otherwise removed from the body.
The half-lives are:
sildenafil (Viagra), 3-4 hours
vardenafil (Levitra), 4-5 hours
tadalafil (Cialis), 17.5 hours
If used for treatment of disease or to fight aging, as opposed to erectile dysfunction treatment, Cialis has an obvious advantage, since it can be taken once a day. Long-term tadalafil was found to be safe and well-tolerated. Note, however, that this study was funded by Lilly, the manufacturer of Cialis.
In a sense, it’s no surprise that PDE5 inhibitors appear to be so effective in treating age-related diseases. Since erectile dysfunction is so closely associated with aging, any drug that restores erectile function is effectively restoring youth, just as a drug that restores insulin sensitivity (metformin) also does.
I expect these drugs to become even more widely prescribed in the future.
Women Find Men’s Strength Their Most Physically Attractive Trait
A question of age-old interest to men is, what do women actually find to be most physically attractive about them? Is it the way they dress, their gestures, posture, a handsome face, beard or lack of one, height, weight? Science has discovered that women find men’s strength their most physically attractive trait.
Strength accounts for 70% of variation in attractiveness
The women not only found the stronger men attractive, but strength accounted for a full 70% of the variation in attractiveness between the men.
Other results include:
Strength was a “robust and much larger predictor of attractiveness than either height or weight”
“Height is attractive even independent of making a man look strong.” Not really news, I suppose.
Weight is unattractive after controlling for how strong a man looks.
Height, weight, and ratings of strength collectively account for 80% of the variance in attractiveness.
I’m surprised at the low ratings of height, and I’m guessing that it could be skewed by the fact of using photographs rather than in-person ratings. But who knows. The authors suggest that height matters to women precisely because it indicates greater strength.
In the case of strength, there was no evidence of a U- or J-shaped curve. Strength was linearly correlated with attractiveness, meaning that in this experiment, the strongest men were the most attractive. Although I wonder what most women have to say about someone like Phil Heath. In my experience, most women say they dislike the big bodybuilder look.
It’s important to note that strength was the most important predictor of physical attractiveness, not mate value. Science shows that women look for many other qualities in a mate, most notably social status.
Why strength is important
There are a couple of plausible reasons why strength is so important to physical attractiveness.
One, it indicates fighting and hunting ability, i.e. the ability of a man to protect and provide for his woman and their children.
Two, it indicates health. Lean muscularity is the ideal state of male health, which is a major theme here at Rogue Health and Fitness. Indicators of health in women are also attractive to men, traits such as long, thick hair, glowing skin, and waist- hip ratio, all of which indicate youth, health, and fertility.
Evolution has made us so, since those who had these qualities left more surviving offspring.
Strength is important for health even in women and even in those who are not young.
Influenza (flu) epidemics occur in winter, and rarely if ever in the summer. Vitamin D levels in humans are lowest in the winter, and highest in summer. Is there a connection, and does vitamin D prevent the flu?
Wintertime flu incidence
Consider the following chart, taken from a paper, Epidemic influenza and vitamin D, which shows the percentage of all cases of type A influenza by latitude and month. Virtually all cases occur in winter and early spring, and none in the summer.
The seasonal and latitudinal distribution of outbreaks of type A influenza in the world, 1964–1975… The diagrams show for each calendar month the percentage of each zone’s total outbreaks. In both north and south temperate zones the epidemics are distributed around the local midwinter, whereas the tropical zones show a transition, each approximating towards the distribution of its own temperate zone. The curve indicates the ‘midsummer’ path taken annually by vertical solar radiation.
Next, the seasonal variation in vitamin D blood levels in people aged 50 to 80 in southern Germany.
There’s a clear correlation between vitamin D and influenza. But is it causal?
Perhaps the flu spreads because people huddle together in close contact in the winter. But, the same people work in offices, take public transport, and attend large gatherings in the summer too, and there’s almost no flu then.
Vitamin D is important for immunity too, giving us further reason to think it’s involved.
A number of other facts lead to vitamin D:
Scandinavians have less flu than the British, and Scandinavians have higher vitamin D levels
Solar flare activity, which decreases solar radiation by increasing atmospheric ozone, is associated with flu epidemics.
Vitamin D deficiency predisposes toward respiratory infections.
Cod liver oil, high in vitamin D, reduces respiratory infections.
Overall, vitamin D showed a protective effect against RTI (OR, 0.64; 95% CI, 0.49 to 0.84). There was significant heterogeneity among studies (Cochran’s Q p<0.0001, I2 = 72%). The protective effect was larger in studies using once-daily dosing compared to bolus doses (OR = 0.51 vs OR = 0.86, p = 0.01). There was some evidence that results may have been influenced by publication bias.
Once-daily vitamin D cut the odds of respiratory infections in half. Average dose was only 1600 IU daily.
That’s good enough for me. Since vitamin D is safe, I see no reason not to take it. In the fall and winter, when I get no sun exposure, I take 5,000 IU on most days. In summer, when I get a decent amount of sun, I don’t take it.
For the record, I last had the flu nearly 7 years ago, and that wasn’t long after I had begun taking vitamin D. I’ve had maybe 2 colds in the past 5 years.
Other factors could influence my low incidence of colds and flu. Being in shape and eating and sleeping well help immune function.
Low vitamin D blood levels may well be the seasonal stimulus for the flu, and supplementing with vitamin D prevents respiratory tract infections.
Vitamin D could prevent a lot of misery, and for some people, even death.
I use NOW brand vitamin D, which uses extra virgin olive oil as a base. Beware of brands that use soy or other seed oils, and many of them do.
Do we get enough vitamin D for good health? Many people are vitamin D deficient, and what’s more, there’s evidence that the amount of vitamin D in supplement form that relieves deficiency is greater than previously thought. How much vitamin D do we need?
The big vitamin D mistake
The big vitamin D mistake is that health authorities, in particular the Institute of Medicine, greatly underestimated the amount of supplemental vitamin D that will make someone vitamin D sufficient, or to keep that person sufficient.
The Institute of Medicine calculated that 600 IU of vitamin D daily would keep most (97.5%) people at a vitamin D blood level of greater than 50 nmol/L, which in more familiar units is 20 ng/ml. However, their calculation was shown to be a mistake.
Without going into all the details (which you can read in the paper), the authors calculated that 8895 IU of vitamin D daily would be needed to get most people above the 50 nmol/L limit. Huge difference. The authors also state, “As this dose is far beyond the range of studied doses, caution is warranted when interpreting this estimate. Regardless, the very high estimate illustrates that the dose is well in excess of the current RDA of 600 IU per day and the tolerable upper intake of 4000 IU per day.”
A different group of scientists confirmed that this estimate was in the ballpark, with about 7000 IU of vitamin D daily, from all sources including the sun, needed to achieve 50 nmol/L in most people.
A meta-analysis of studies on vitamin D and mortality showed an inverse correlation between vitamin D blood levels and death rates. See chart below. At vitamin D levels that indicate clear deficiency, death rates were almost twice as high as when blood levels were normal.
The meta-analysis found that the point at which higher levels were no longer associated with lower death rates with statistical significance was 36 ng/ml, or about 90 nmol/L. Assuming this analysis is correct, people should strive for blood levels at least that high. That’s about 80% higher than what the Institute of Medicine recommended.
A pediatrician, Dimitrios T. Papadimitriou, calls the calculations of the Institute of Medicine the Big Vitamin D Mistake. He writes:
Since all-disease mortality is reduced to 1.0 with serum vitamin D levels ≥100 nmol/L, we call public health authorities to consider designating as the RDA at least three-fourths of the levels proposed by the Endocrine Society Expert Committee as safe upper tolerable daily intake doses. This could lead to a recommendation of 1000 IU for children <1 year on enriched formula and 1500 IU for breastfed children older than 6 months, 3000 IU for children >1 year of age, and around 8000 IU for young adults and thereafter. Actions are urgently needed to protect the global population from vitamin D deficiency.
Note that these amounts of vitamin D are from all sources put together: sun, food, and supplements.
A review on vitamin D intake concluded that the maximum safe dose, or Tolerable Upper Intake Level, is 10,000 IU daily. That doesn’t necessarily mean that this is the best dose, but that no toxicity has been seen in human clinical trials at that dose. Higher doses of vitamin D can be toxic. In contrast, the Endocrine Society recommends an upper limit of 4,000 IU daily.
Low blood levels of vitamin D are associated with higher death rates.
The amount of vitamin D needed to attain levels associated with better health have been underestimated.
The only certain way to know whether you have adequate vitamin D is through a blood test.
Getting vitamin D through sun exposure is the best way to get enough vitamin D, one reason being that sun exposure has other benefits. But as we saw above, for many people, there’s not enough sun to increase vitamin D blood levels outside the summer months.
Strong Bones Improve Brain Function and Slow Aging
Strong bones are usually thought of in the context of osteoporosis, the pathological thinning of bones in old age. Osteoporosis can be fatal, since it leads to hip fractures, a large fraction of which lead to death within a year. New evidence is coming to light that bones are an endocrine organ that secretes hormones that are vital for health, and that strong bones improve brain function and slow aging.
Osteocalcin, the rejuvenating factor in young blood
Osteocalcin declines with age, and is thought to be behind not only the changes in bone with aging, but, as seen in the above-cited studies, many other functions including increased insulin resistance and decreasing muscle mass.
In the same study in which scientists injected osteocalcin into old mice, they injected plasma from young mice into older mice, and this significantly alleviated cognitive deficits. Plasma from other old mice did not.
Plasma from young osteocalcin knockout mice, which contains none of the hormone, had no effect either.
Plasma from wild-type mice which had been depleted of osteocalcin (using antibodies) also had no effect.
Plasma from osteocalcin knockout mice that had been spiked with recombinant osteocalcin did increase cognitive function. Ergo, osteocalcin is at least one of the factors in young blood that causes rejuvenation.
The investigators state, “Together, these experiments indicate that OCN [osteocalcin] is a necessary contributor to the beneficial effect of plasma from young WT [wild-type] mice on hippocampal-dependent memory and anxiety-like behaviors in older WT mice.”
It seems likely that recombinant osteocalcin could be used to rejuvenate humans. No necessity for transfusions from young people. Weekly injections, similar to that for testosterone therapy, might work. Once manufacturing scaled up, there’s no reason it wouldn’t be cheap too.
Bones produce osteocalcin during remodeling and growth. This hormone is only now beginning to be understood.
Osteocalcin has profound beneficial effects on brain function in lab animals.
Osteocalcin increases insulin sensitivity, and is at least partly responsible for the rejuvenating effect of young blood. Recombinant osteocalcin, which could be injected, could become important as an anti-aging therapy, in my opinion. We’ll just have to wait and see.
Meanwhile, keep bones strong via weight-bearing exercise. Resistance (strength) training is the most beneficial for bones, and ought to be the best for maintaining high levels of osteocalcin.
By the way, vitamin K2 is necessary to activate osteocalcin for bone remodeling, although as far as I can see, may not be necessary for improvements in brain and insulin function.
Low Testosterone Is Associated with Insulin Resistance
Testosterone (T), the hormone that gives men their male sex characteristics, declines with age. T is also declining over time, i.e. a men of any age have lower T levels than men the same age 20 or more years ago. Could one factor explain both types of decline? The fact that low testosterone is associated with insulin resistance argues for an answer in the affirmative.
The authors of the above-linked article note the same question and state that “the finding, in some studies, that T levels did not fall significantly with age in exceptionally healthy men raised the question of the relative roles of chronic age-related illness vs. aging per se in producing the observed decreases.” [My emphasis.]
In fact, in one study (cited here) men aged 80 to 89 in the upper 2.5 percentile has T levels averaging 964!
Clearly, decline of T with age is not a foregone conclusion. Good health can keep T levels high, at least in some – and I would argue, most – cases.
Low testosterone is common in type 2 diabetics, with some 47% having T levels that indicate hypogonadism. However, hypogonadism is defined by a number which, while it isn’t totally arbitrary, represents a binary division, whereas T levels are on a spectrum. In other words, insulin resistance impacts the T levels of all men, not just diabetics, and just because one isn’t deemed clinically hypogonadal doesn’t mean that one’s T levels are optimal, or all that they could be.
In blood donation, the removal of blood leads to lower body iron stores, since iron must be removed from storage to replenish the red blood cells lost during donation. Hemoglobin, the oxygen-carrying molecule of red blood cells, requires iron as a necessary co-factor.
Regular blood donors have lower body iron stores than non-donors, on average. (“On average” because certain groups, especially fertile women, have relatively low body iron. Fertile women are also much less prone to disease than men the same age or older women.)
It follows that blood donors ought to have better insulin sensitivity. Turns out that they do.
A problem in studies of blood donors, as I discussed in my book Dumping Iron, is a so-called healthy donor effect. Blood donors are more likely to be healthier than non-donors, since if they are unhealthy they can’t donate, and this could account for some of the better health seen in donors.
A number of ways exist to get around the healthy donor effect to see whether blood donation truly causes better health, or whether there’s a mere association between the two.
In this particular study, donors were carefully matched with non-donors for “age, body mass index, waist-to-hip ratio, and cardiovascular risk profile, including blood lipids, blood pressure, and smoking status.” This matching could eliminate much or all of the healthy donor effect, if the participants were alike in every way except the fact of being blood donors.
Blood donors also had lower ferritin levels, which measures body iron stores. The ferritin of donors averaged 101 μg/L, that of non-donors was 162.
Much experimentation and speculation has gone into trying to explain how metformin works.
It turns out, according to a recent study, that metformin induces an iron deficiency-like state. In effect, metformin causes an organism to “believe” it’s in a state of low iron, which upregulates certain cellular processes that are known to prolong lifespan.
Cold thermogenesis, or the generation of heat through exposure to cold, has become popular recently, or as popular as something like this can become. What’s the reality and how much is hype behind cold thermogenesis?
How cold thermogenesis works
Cold thermogenesis is the production of body heat during and after the body has been exposed to cold. The body must produce heat when exposed to cold, since all physiological and biochemical systems are designed to work at an optimal temperature, around 37° C. or 98.6° F.
In extreme cases, it’s a matter of survival.
There are two ways the body uses to increase the metabolic rate and produce heat: one is through the muscles and shivering, the other is through the activation of brown fat.
Brown fat is a metabolically active form of adipose (fat) tissue. The majority of fat tissue in adults is white adipose tissue, which is relatively metabolically inactive. Until recently, it was thought that only infants and children carry substantial amounts of brown fat, but it’s been discovered that adults have it as well.(1) Cold exposure activates brown fat.
In people who have brown fat, or enough of it to be detectable, cold exposure causes an increase in the metabolic rate.
Exposure to an air temperature of 19 C. (66 F.) while wearing light clothing (t-shirt and underwear) caused an approximately 30% rise in energy expenditure – basal rate was 1446 calories a day, and this increased by 410 calories. The BAT (brown adipose negative) group rise was only about 40 calories.
If this increased energy expenditure were to be repeated often enough, large amounts of calories would be burned. But to burn an extra 400 calories a day, presumably you’d have to sit in a cold room in your underwear 24 hours a day.
Water has a high heat capacity, higher than air, meaning that in cold exposure, water will make the body colder in less time than air. Cold water exposure is therefore a more efficient way to cool the body; it’s also more efficient at killing people at extreme temperatures than air. (Allegedly, a pilot who ditched in the North Sea during WW2 had only a minute or two to get out of the water before he died.)
So, what happens to people in cold water exposure? Immersion of the entire body, with head out, in water of 20 C. (68 F.) causes a near doubling (93%) in the metabolic rate. If that were continued over 24 hours, that might mean 1500 more calories burned.(2)
Exposure to cold water at 14 C. (57 F.) ramped up the metabolic rate by 350%, or 4.5 fold. That’s the equivalent of an extra 6750 calories daily, or around 280 calories an hour.
Cold showers have the potential to treat depression, chronic fatigue, and possibly even cancer, through their effects on the immune system. Cold showers will not be as effective as complete immersion in cold water for raising the metabolic rate, but they offer a reasonably good alternative.
I take a cold shower daily. I recently (November) measured the temperature of the water in my shower, and it was 66 F. (19 C.) That temperature feels cold enough when you first step into it, but you get used to it quickly and it soon feels normal. The temperature of shower water varies a good deal, depending on your local conditions, and could be much colder or warmer. My January water temperature is around 55 F. (13 C.)
We saw above that a one-hour exposure to air of about the same temperature as the water in my shower caused an approximate 30% increase in metabolic rate. Since water is more efficient than air in this respect, we might guess that 5 minutes in a cold shower would have the same effect. While this is guesswork, judging by my subjective experience, it’s in the ballpark.
Other than coffee, there’s nothing like a cold shower to get you going in the morning. They take you from that soft cocoon of warmth and sleepiness to ready to take on the day. But will they help you burn fat?
If my metabolic rate increases 30%, and that lasts an hour (which may be generous), then I burn an extra 21 calories through cold showering. So no, that’s not going to help me burn fat.
If I were to take a shower at a colder temperature, 57 F. (14 C.), and stay in for an hour, and the increase in metabolic rate lasted two hours (again, probably generous), then I might burn an extra 560 calories. Now we’re getting somewhere – but unless you do this daily, it’s not likely to make a lot of difference in calories burned.
Cold vs exercise
People seem to be interested in the topic of cold thermogenesis as a way to increase calories burned without actually doing anything. In other words, increase your metabolic rate and you’ll burn more fat just sitting there. But there are a couple of problems with this notion.
One is that exercise burns a lot more calories than any reasonably credible increase in metabolism through cold exposure.
The amount of energy expenditure through exercise is often measured in terms of metabolic equivalents, or METs. A MET is the increase in energy expenditure as a ratio of basal metabolic rate. Sitting quietly has a MET of 1.0. Brisk walking and tennis both have a MET of 5, jogging and cycling a MET of 10. Other high-intensity exercises have a yet greater effect, sprinting or jumping rope, for instance.
Even moderate exercise increases the metabolic rate quite a bit more than exposure to very cold water. If you wanted to burn more fat, you’d be better off going and playing tennis for an hour than you would taking a cold shower for the same length of time.
Furthermore, a game of tennis is bound to be more enjoyable.
The final objection to the notion of increasing metabolic rate to burn fat is the same as with exercise: it’s very easy to make up for what you have burned by eating more. Aerobic exercise has a poor record at fat loss, so poor in fact that most actual experts say it does next to nothing. (I discussed this extensively and cited relevant studies in my new book, Muscle Up.)
Increased metabolism has no advantage over exercise in this regard; it is not magic. If you don’t control your food intake, then nothing you do in the way of either exercise or increased metabolism will matter much for weight loss.
Like exercise, increasing the metabolic rate will have similar beneficial effects on health. But unfortunately, fat loss isn’t one of them.
Increasing brown adipose tissue (BAT)
As I discussed in my book, there is an exception to the rule that exercise doesn’t cause fat loss, and that is resistance training (strength training, weightlifting). The reason that this form of exercise works is because it builds muscle and reduces insulin resistance; muscle has a higher metabolic rate than fat tissue, and better insulin sensitivity allows for fat to be burned off more readily.
By increasing the amount of actively metabolic tissue (muscle), weightlifting causes more calories to be burned even at rest. Weightlifting has been shown to be much more effective for fat loss than aerobic exercise – albeit watching one’s food intake is still important.
Brown adipose tissue, as we saw above, burns more calories than white adipose tissue; BAT appears to be the main component of increased metabolic rate, short of shivering, which is a function of the muscles. Therefore if we increase the amount of BAT, this will, just like the addition of muscle, burn more calories around the clock. But can this be done?
There are some indications that it is possible to increase BAT. A group of people, aged 20 to 73, underwent cold exposure and were tested for the presence of BAT.(3) Among people in their 20s, more than half of them tested positive for BAT, but among people older than 60, that figure dropped to 10%. Furthermore, those who tested positive for BAT had a lower BMI, and less body and abdominal fat.
So there’s some indication not only that more BAT means less body fat, but that the incidence (and presumably, the amount) of BAT declines with age. If BAT declines with age, that means that certain measures may be able to combat the loss of BAT, just as certain measures can combat other aspects of aging.
Inactive or inefficient BAT is also seen in obesity.(4) So an increase in quality – likely meaning better mitochondrial function – may also mean less body fat.
Since cold exposure causes more BAT activity, it stands to reason that repeated cold exposure may increase the amount of BAT. Whether it actually does so is not known.
As for increasing BAT quality, anything that improves mitochondrial function should help. That includes exercise, and supplements like resveratrol and curcumin. A diet low in carbohydrates should help too.
Certain food ingredients and other supplements also activate BAT(5), including capsaicin, cinnamon, black pepper, and green tea catechins.
Certain figures in the world of biohacking have generated a lot of hype about cold thermogenesis, probably because it’s new and different and people are desperately seeking solutions for fat loss. As we’ve seen, cold thermogenesis isn’t a panacea by any means. It’s generated at the cost of quite a bit of discomfort, and whether it will truly result in fat loss, and how BAT may be related to the obesity epidemic, are all but unknown.
My take on this is that cold exposure, such as a cold shower, has decided benefits, just as exercise does. But if not combined with a decent diet then one should not expect fat-loss miracles.
(Article updated 11/26/2017.)
PS: For more on exercise and fat loss, pick up a copy of my book, Muscle Up.
Why You Should Never Feed Your Child Commercial Infant Formula
Commercial infant formula is an abomination, a concoction of chemicals and industrial “food” that you should never feed your child. Here’s why.
Over the Thanksgiving holiday, I came across a “food product” called Enfagrow that a relative was feeding her one-year-old boy. Enfagrow is meant to be given to toddlers age 1 to 3 after weaning, and is billed as “Toddler Next Step”.
Here are the ingredients:
The first 3 listed ingredients are non-fat milk, corn syrup solids, vegetable oil. Then following are some chemicals, a multivitamin and mineral supplement, natural flavor, and soy lecithin.
Non-fat milk (in this case, it’s also powdered) has all the healthy milk fat removed. Milk fat contains EPA, DHA (both omega-3 fatty acids) and conjugated linoleic acid, a potent anti-cancer molecule. Skim (non-fat) milk is used to fatten pigs. Think it might have the same effect on children and other people? I do.
The daily exposure of infants to isoflavones in soy infant-formulas is 6–11 fold higher on a bodyweight basis than the dose that has hormonal effects in adults consuming soy foods. Circulating concentrations of isoflavones in the seven infants fed soy-based formula were 13 000–22 000 times higher than plasma oestradiol concentrations in early life, and may be sufficient to exert biological effects, whereas the contribution of isoflavones from breast-milk and cow-milk is negligible.
As Dr. Greiner remarked over on twitter, it’s like giving your child 5 birth control pills daily. A huge exposure to estrogenic compounds.
These two products together might be called the Diseases of Civilization Starter Pack. Lifelong exposure to so-called “food” like this will lead to obesity, diabetes, cancer, and heart disease. Can’t get ’em started on the road to diabesity too young.
Unfortunately, not only does Big Food not care a whit about your or your children’s health, but most people just accept these chemical concoctions as par for the course. Personally, I wouldn’t feed them to a dog.
Usually I write about men’s health and fitness in these pages, but this is an important issue. men have children, and presumably they (and the mothers of their children) want them to grow up to be healthy, lean, and with no endocrine problems. Be aware of these industrial abominations called infant formula.
PS: If you liked this post, pick up one of my books, like Dumping Iron.