Oct
08
2016

Vitamin D3 Protects Your Brain

More and more studies are showing that vitamin D3 protects your brain. It protects against MS, but also against Parkinson’s disease and Alzheimer’s disease. In the following I will review what evidence there is to support each of these topics.

Vitamin D3 protects your brain from multiple sclerosis (MS)

It has been known for some time that in the northern hemisphere MS is more common because of the lack of sunshine, which in turn produces less vitamin D3 in the skin.

MS is an autoimmune disease where immune cells attack the lining of nerves. Both nerve cells and immune cells have vitamin D receptors. It appears that immune cells are calmed down by vitamin D3 and remission of an MS relapse is more likely.

There are two forms of MS, the relapsing-remitting MS and the progressive MS. The first one (relapsing-remitting) is more common. After a bout of active MS, the illness calms down and the condition of the patient is stable for some time until the next relapse occurs.

With progressive MS there are two forms, primary progressive MS and secondary progressive MS. The primary form is a case of MS where symptoms steadily worsen, without any remission. The secondary form of progressive MS occurs at the end of fairly stable relapsing-remitting MS. Symptoms become more pronounced and the condition deteriorates steadily from there.

Progression and disability in MS patients with various vitamin D3 levels

Dr. Fitzgerald and colleagues published a study in JAMA Neurology in 2015.

They took 1482 men and women who were on interferon beta-1b treatment. This treatment utilizes the immunomodulator interferon beta-1b and reduces the number of relapses in patients with MS. The study took place between November 2003 and June 2005. Results were analyzed between June 2013 and December 2014. The researchers measured vitamin D levels (as 25-hydroxy vitamin D). The vitamin D levels were obtained at baseline, at 6 months and 12 months.

The number of brain lesions were measured by MRI scans. All of the patients also underwent a functional test, called expanded disability status scale. This measured impairment of ambulation, ability to communicate and activity levels.

Results of this study showed marked differences between patients with high and low vitamin D levels. Those patients who had the highest vitamin D blood levels (more than 40 ng/mL) had the lowest rates of new MS lesions. Previous studies had found that a low blood level of vitamin D (less than 25 ng/mL) in patients was associated with a much higher risk of developing MS. Dr. Fitzgerald’s study showed that a 50.0-nmol/L increase in serum vitamin D levels associated with a 31% lower rate of new MS lesions. Patients with the highest vitamin D level of more than 100 nmol/L had the lowest amount of new MRI lesions (47% less than the patients with the lowest vitamin D levels).

Another study showed that a low-dose vitamin D level accelerated MS. There was a 5.9-fold risk converting the initial relapsing-remitting form of MS into the secondary progressive form of MS.

All these studies show that vitamin D3 can decrease the risk of getting MS. In addition vitamin D3 also delays progression in those who have MS.

Vitamin D3 protects your brain from Parkinson’s disease

Vitamin D3 plays a role in preventing Parkinson’s disease.

Parkinson’s disease is a neurodegenerative disease that causes tremor in muscles, causes balancing problems and eventually can lead to dementia. A metaanalysis was done in 2014 and 7 studies where identified to be relevant. The authors were looking for correlation of vitamin D levels with Parkinson’s disease. 1008 patients were included in the metaanalysis with 4,536 controls.

  • Patients with a vitamin D level of less than 75 nmol/L had a 1.5-fold higher risk of developing Parkinson’s disease than the controls.
  • Patients with a vitamin D level of less than 50 nmol/L were at a 2.2-fold higher risk of developing Parkinson’s disease.

Another metaanalysis utilized 5,690 Parkinson’s disease patients and 21251 matched controls.

It found that vitamin D levels of less than 20 ng/ml were associated with a risk of 2.08-fold to develop Parkinson’s disease. Interestingly, vitamin D3 supplementation reduced the risk of Parkinson’s disease by 38%. Outdoor work reduced the risk of developing Parkinson’s disease by 28%.

Vitamin D3 protects your brain from Alzheimer’s disease

Alzheimer’s disease is a neurodegenerative disease of old age. We know that it is much more common in patients with type 2 diabetes where insulin levels are high. Studies have shown that Alzheimer’s disease can be termed type 3 diabetes.

The resulting neurofibrillary tangles and amyloid-beta deposits damage nerve cells, which are responsible for the memory loss and the profound personality changes in these patients.

What does vitamin D3 have to do with this?

A 2014 study showed that a low vitamin D level was associated with a high risk of dementia and Alzheimer’s disease.

Specifically the following observations were made.

  • Vitamin D level of less than 10 ng/ml: 122% increased risk of Alzheimer’s
  • Vitamin D level 10 to 20 ng/ml: 51% increased risk of Alzheimer’s

The same research group found in two trials that vitamin D deficiency leads to visual memory decline, but not to verbal memory decline.

Vitamin D3 combined with metformin suppresses cancer

The newest development with respect to vitamin D3 is the finding that it also has anti-cancer effects. Dr. Li demonstrated that vitamin D reduced prostate cancer cell line growth by 45% while metformin alone reduced it by 28%.

But when both vitamin D and metformin were present in the cell cultures there was growth inhibition of 86%. Dr. Li explained that vitamin D potentiated the growth inhibitory effect of metformin.

Vitamin D3 protects your brain: guidelines to proper vitamin D3 dosing

For years the medical profession stated that 400 IU of vitamin D3 would be enough supplementation. It may be enough to prevent rickets in children. But these low doses will be insufficient in many patients who are deficient for vitamin D to prevent MS, Parkinson’s disease, Alzheimer’s disease or cancer.

A study on medical staff in Northern India showed that 85% of the staff had very low vitamin D levels of less than 10 ng/ml.

It took high doses of vitamin D3 to increase the vitamin D level in the blood.

Generally supplements of vitamin D3 of 5000 IU to 8000 IU are the norm now. But some patients are poor absorbers and they may require 15,000 IU per day. What the patients need can be easily determined by doing repeat vitamin D blood levels (as 25-hydroxy vitamin D). The goal is to reach a level of 50-80 ng/ml. The optimal level with regard to nmol/L is 80 to 200 (according to Rocky Mountain Analytical, Calgary, AB, Canada).

Vitamin D3 Protects Your Brain

Vitamin D3 Protects Your Brain

Conclusion

Many people are deficient with regard to vitamin D, and they do not know it. The most important thing is to do a vitamin D blood test to assess your vitamin D status.

We know for a long time that vitamin D plays a role in bone metabolism and this is why women approaching menopause often need vitamin D3 supplementation. But it may come to you as news that vitamin D3 also protects from MS, Parkinson’s disease and Alzheimer’s disease. In addition, as indicated above, we know that many cancers are suppressed by taking vitamin D3 regularly.

When you realize that all body cells have vitamin D receptors on their surface, it is no surprise that vitamin D3 is so important to take. The vitamin D3 receptors must be there for a reason. If your body is deprived of this valuable vitamin, the high risk of degenerative diseases will be the consequence.

May
31
2014

Industry Sponsored Diet Soda Study Deceptive

Recently an industry sponsored study was reviewed by the media with this headline: “Diet soda helps weight loss, industry-funded study finds”. Before you get too excited about this study, let me tell you that you are being deceived. Essentially the study compared 150 overweight or obese people on water and a similar group of people on diet sodas. Both groups were counselled on the benefits of exercise and a healthier diet. At the end of 12 weeks the water group that did not drink diet sodas had lost 9 pounds, while the diet soda group that continued their former habit lost 13 pounds. The question now is why this 4 pound difference? The sponsor of the study would like you to think that the soda diet drink is healthier, because it helps you to lose weight. Let me explain to you that there are a few flaws in the study as follows.

1. Most often there are confounding errors in industry-sponsored studies. Even though it looks on the surface that the two groups were comparable, researchers should have checked out various parameters like sex distribution, other underlying illnesses, mental state (depressed or not etc.), diabetes and other factors to make sure that there is no metabolic bias between the two groups from the start of the study.

2. Deception built into study: we know from other studies that on the long-term diet sodas lead to weight gain by stimulating your appetite for sweets and their subsequent consumption. Often short-term studies show the opposite effect, so it would be false to assume that long-term results would be similar. But most readers who read this quickly would be tempted to think “so it must be OK to continue to consume diet soda drinks!” Off you go to the grocery store and buy another 6 or 12 pack. That’s exactly what the industry-sponsored study set out to do. Somewhere in the back-room of a big soft drink corporation the executives discussed among themselves that their statistics were bad; the sales of diet soft drinks were down; there was too much negative press fuelled by the health food industry. They had to do something about this, so they designed a study where the good guy was the diet soft drink. If the consumer is not buying the results, at least the study helped to confuse people and whenever there is confusion, at least part of the confused population will return to their old habits. After all the study showed “ it is OK”.

Industry Sponsored Diet Soda Study Deceptive

Industry Sponsored Diet Soda Study Deceptive

3. Excitotoxins are not OK. Unfortunately all artificial sweeteners are toxic to your brain, they are excitotoxins. MSG is another excitotoxin. The only exception is the natural sweetener stevia, a plant product, which is OK. Splenda is an insecticide, so this is belongs to the xenoestrogens, bad for you as it acts like a foreign estrogen and has cancer-promoting qualities when exposed to it for several decades. The rest of the artificial sweeteners are excitotoxins: they burn your brain cells very slowly and can lead to dementia. Unfortunately they are addicting and your brain will make you feel good when you drink more of it. So, the real reason why the study group on diet sodas did better than the water group is because they did not have to change that habit, there was no withdrawal to deal with and they felt fine. So they could concentrate on dieting and exercising and of course you would lose 13 pounds in 12 weeks doing that. The water group on the other hand had to cope with diet soda withdrawal and on top was challenged by an exercise and weight loss program. As there was no diet restriction, they could compensate a bit for their trouble of withdrawal and eat a few muffins or some extra bread to make up for the lack of their comfort diet drink fix (the satisfaction of consuming the excitotoxin). This slick short-term study design is what should have alarmed the publisher to ask a few hard questions.

4. There needs to be an internal logic in the study: Let’s do a thought experiment where we repeat the study and start with two comparable overweight/obese groups of people and put them on no sugar and no refined carbs for 2 weeks and also on no diet sodas for the same time. After two weeks they are both accustomed to this diet and the no diet soda habit and they have probably lost the same amount of weight from the calorie restriction. Now we start the one group on diet sodas and the other group on water, but strictly controlled for a similar calorie intake in terms of other foods or drinks as much as is humanly possible. I would predict that after 12 weeks the water group will have at least lost the same weight as the diet soda group, if not more. The diet soda group likely will have had some problems with sugar craving and may have had more dietary indiscretions (sneaking in snacks and underreporting them), but this would show up as weight gain.

You may be proud of having completed this well controlled study. The trouble is that your industry sponsor that produces the diet drinks will not like this outcome and would not allow the results to be published. In fact that kind of result would be actively suppressed.

Conclusion:

The diet soda study discussed here is a lesson in biased publishing. We are constantly bombarded by an endless string of meaningless publications that are designed to make the consumer insecure, or bias us for accepting a company’s product in the hope of achieving a certain result (like high sales). Even, if this is not accomplished the company has sold enough of their product just for giving it a try. Beware of the door-to-door sales person. This figure is very much present right in this publication. In this case it is the sales pitch of the diet soda manufacturers! You are looking at a study that was designed to make you buy more of the excitotoxin (aspartame or other artificial sweeteners), which likely contributed to your extra weight or obesity in the first place. It’s up to you to shut the door on this sales pitch. Instead of a diet soda I suggest you make your own drink: squeeze half an organic lemon and top this with mineral water of your choice. Sweeten it with a tiny amount of stevia. This has no calories and does not stimulate you to eat more sugar and starchy foods; but it quenches any thirst and you even get some water-soluble vitamins in the process.

Last edited May 31, 2014

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May
10
2014

The Full Story About Testosterone

Much has been written about what happens when women get into menopause. This begs the question: do men experience a change of life? As a matter of fact, they do. It is called “andropause”, and they can experience problems as a result. Here is a study from the Massachusetts General Hospital in Boston, MA, which was published in the New England Journal of Medicine (Sept. 2013) describing in detail what happens when men get into andropause (the male equivalent of the menopause).

We know from other studies that in obese men testosterone is converted into estrogen because of the enzyme aromatase that converts testosterone into estrogen resulting in erectile dysfunction and loss of sex drive. In lean men above the age of 55 there is a true testosterone reduction because the testicles produce less testosterone. This results in less sex drive, moodiness and lack of energy. But these men will do well with bioidentical testosterone replacement.

Main findings of the Massachusetts General Hospital study:

  1. Testosterone was responsible for thigh muscle development and leg press strength, for erectile function and sexual desire.
  2. Surprisingly, estradiol (the main estrogen component in both sexes) plays a significant part in sexual desire in the male. This became particularly apparent in the post-andropause male who desired hormone replacement. When bioidentical testosterone is used to replace what’s missing there was no problem with sexual desire or erectile function as a small amount of the testosterone was aromatized into estradiol. The researchers were able to measure both testosterone and estradiol levels.
  3. Here is a surprising fact: a lack of estrogen leads to abdominal obesity. This could also be verified by hormone measurements.
  4. In the past doctors used synthetic testosterone products like methyltestosterone, danazol, oxandrolone, testosterone propionate, testosterone cypionate or testosterone enanthate. The problem with these synthetic testosterone products is that the body cannot metabolize a portion of them into estrogen that is desirable for a normal sex drive, so the testosterone compounds alone are not doing their job as well as the bioidentical testosterone that the body can aromatize.

In obese men the problem is that there is too much estrogen in the system, which leads to a disbalance of the hormones in the male with a relative lack of testosterone. Overweight and obese men produce significant amounts of estrogen through aromatase located in the fatty tissue. Aromatase converts testosterone and other male type hormones, called androgens, into estrogen. Excessive levels of estrogen cause breast growth, muscle weakness, lead to abdominal fat accumulation, heart disease and strokes. Dr. Lee described what happens in men who enter andropause years ago as indicated under this link.

The Full Story About Testosterone

The Full Story About Testosterone

Testosterone to estrogen ratio:

Dr. Lee indicated that in his opinion saliva hormone testing is more reliable than blood tests (Ref. 1). One of the advantages of doing saliva hormone tests of estrogen and testosterone is that you can calculate directly the ratios of these two hormones. In hormonally normal younger males the testosterone to estrogen ratio is larger than 20 – 40 (Ref.2). The testosterone to estrogen ratio in obese men is typically less than 20 meaning it is too low. But lean men in andropause produce too little testosterone and their testosterone to estrogen ratio is also less than 20, because they may still have enough estrogen in their system from aromatase in the fatty tissue, but they are lacking testosterone due to a lack of its production in the testicles (Ref. 1 and 2).

When a man in andropause is given bioidentical hormone replacement with a testosterone gel or bioidentical testosterone cream this is absorbed into the blood and body tissues and then partially metabolized into a small amount of estrogen. This can be seen when saliva hormone tests are done; a higher level of testosterone is detected and much lower estrogen level so that the testosterone to estrogen ratio is now 20 to 40 or higher and the affected person will no longer be the “grumpy old man” that had been a source of distress to his partner before.

This New England Journal of Medicine study is important because it confirmed what anti-aging physicians had been saying for years: a small amount of estrogen is necessary for the male for bone health as estrogen receptors will regulate the bone density, it also helps for a normal sex drive. The same is true for women: a small amount of the opposite hormone (testosterone) will help a woman’s sex drive, but she needs the right mix of progesterone to estrogen (a progesterone to estrogen ratio of 200:1 using saliva tests) to feel perfectly normal as a women.

Health and well-being of a man depend on normal testosterone levels:

It is important to realize that testosterone is not only supporting a man’s sex drive and libido, key organs like the heart, the brain and blood vessels contain testosterone receptors as well. The body of a man was designed to respond to testosterone all along. It is when testosterone production is no longer keeping up that premature aging becomes apparent, as the target organs do no longer receive the proper signals.

A healthy heart in a man depends on regular exercise and testosterone stimulation whether he is young, middle aged or old. The same is true for the lining of the arteries where testosterone receptors are present to help with the normal adjustment to exercise and relaxation. The brain cells have receptors for all of the sex hormones and in a man they are used to higher levels of testosterone and lower levels of progesterone and estrogen. If you take the balance away, the aging man will feel miserable and grumpy. Depression will set in. Here is a brief review how one man’s life has been changed by testosterone replacement.

So, bioidentical hormone replacement is not just a matter of replacing one hormone, you need to pay attention to all of the hormones. Lifestyle issues enter the equation as well. I have reviewed the issue of bioidentical hormone replacement for women and men in this blog.

Conclusion:

When a man reaches the age of 55 or older there comes a point where a lack of testosterone and estrogen sets in. It is wise to start doing intermittent blood or saliva hormone tests before this point is reached in order to gage when bioidentical hormone replacement treatment should be given. Along with an assessment regarding the hormone status it would be wise to also assess lifestyle issues as often other factors play a role in premature aging. I have reviewed these factors systematically in a recent publication (Ref. 3). It is best to combine bioidentical hormone replacement with life style interventions to achieve optimal preservation of a man’s health.

More information about male menopause (=andropause): http://nethealthbook.com/hormones/hypogonadism/secondary-hypogonadism/male-menopause/

References:

  1. John R. Lee, MD: “Hormone Balance for men- what your doctor may not tell you about prostate health and natural hormone supplementation”. 2003 by Hormones Etc.
  2. George Gillson, MD, PhD, Tracy Marsden, BSc Pharm: “You’ve Hit Menopause. Now What?” 2004 Rocky Mountain Analytical Corp. Chapter 9: Male Hormone Balance (p.118-148).
  3. Dr.Schilling’s book, March 2014, Amazon.com:“A Survivor’s Guide To Successful Aging: With recipes for 1 week provided by Christina Schilling”.

Last edited Nov. 8, 2014

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Apr
30
2014

Overuse Of Supplements Can Create Health Risks

The Dietary Supplement Health And Education Act of 1994 made it easier for people to acquire supplements and vitamins from health food stores. But since then there has been a proliferation of various products that are sold as supplements and not as drugs. It may give you the impression that all supplements are harmless, but this is not so. There are some supplements like vitamin A where you need to watch that you are not inadvertently overdosing, as toxicity is a problem; calcium supplements are also potentially toxic, if overdone. And amino acid supplements (protein supplements) can lead to an overdose of brain hormones. Here is a sample of some of the supplements that I would want you to watch.

1.Vitamin A toxicity:

Vitamin A is essential for normal night vision, for red blood cell production in the bone marrow and for the immune system. Here is a brief review about its metabolism. But while small amounts are beneficial for the body, high doses are toxic. In the 19th century the Arctic explorer Elisha Kane reported that consumption of polar bear liver caused severe headaches, drowsiness, irritability and vomiting within a few hours of ingesting it.

It is now known to be due to “pseudotumor cerebri”, a condition that mimics a brain tumor, but is caused by an acute overdose of vitamin A contained in liver (Ref. 1).

In the US where people eat enough meat, fish and dairy products, there is no overt vitamin A deficiency. Read this link to avoid overdosing with vitamin A in multiple supplements.

Overuse Of Supplements Can Create Health Risks

Overuse Of Supplements Can Create Health Risks

2. Vitamin C:

Vitamin C is an important antioxidant vitamin and is needed as a co-factor for many metabolic reactions. It is participating in the production of collagen and connective tissues, helps with fatty acid transport and is necessary for the synthesis of neurotransmitters in the brain (Ref.2). The lack of vitamin C is known as scurvy; symptoms include bleeding gums from fragile capillaries, delay in wound healing and impaired bone metabolism. Although in the earlier research it was hoped that vitamin C would prevent colds and cure cancer, more recent reevaluations found that it does not prevent you from getting colds, but it accelerates the recovery from colds by cutting down the recovery time by as much as 25 to 30% and it also does have some cancer protective effects (Ref.2). Higher doses seem to be more beneficial, but 1500 mg per day seems to now be the consensus of a reasonable upper dose limit per day.

What about kidney stones? Several studies in the past have warned about vitamin C being broken down in some people into calcium oxalate kidney stones. Here is a brief review of the literature with regard to kidney stone formation. A study regarding the DASH diet, which is used for people with high blood pressure, showed that the incidence of kidney stones is almost half for both men and women compared to controls on a normal North American diet.

There has been a concern among the medical community that vitamin C as a supplement would increase kidney stones (oxalate stones). However a 2014 study showed that when both vitamin C and vitamin E are taken as supplements, the kidney stone formation goes down.

Many inhabitants of industrialized countries including the population in the US and other countries are magnesium deficient and this can be a major factor for forming calcium oxalate stones. But it has been known for decades that those who develop kidney stones excrete more oxalates in their urine (so-called “oxalate excreters”). Here is a 1996 study that measured this in detail.

If you are taking in a lot of green smoothies from green leaf vegetables (spinach, kale, Swiss chard) that are high in water-soluble vitamins, you may not require any vitamin C supplements. In other words, think about what else you do and eat and add it up, so you do not exceed a total of 1500 mg to 2000 mg of vitamin C per day.

If you are taking in a lot of green smoothies from green leaf vegetables (spinach, kale, Swiss chard) that are high in water-soluble vitamins, you may not require any vitamin C supplements. In other words, think about what else you do and eat and add it up, so you do not exceed a total of 1500 mg of vitamin C per day.

3. Calcium supplements:

Calcium is a key mineral in the body, important not only for healthy bone structure, but also to balance the electrolytes within the blood, in the extra cellular fluid space and within our cells. If calcium is low, the brain is more prone to seizures and the heart can produce dangerously irregular heart beats. We definitely need a balance of calcium! Because calcium is so central to our wellbeing, several factors work together to keep our calcium levels stable: the kidneys, the thyroid, the parathyroid glands, the adrenal glands, the bone as a reservoir of calcium, the gastrointestinal tract for absorption and a good, balanced nutrition. The chapter on “Vitamins and Minerals” of Ref.3 points out that 4000 mg of calcium per day definitely causes toxicity (hypercalcemia and milk-alkali syndrome).

Absorption is dose dependent meaning that only 500mg of calcium carbonate is absorbed at a time. Vitamin D3 deficiency leads to reduced calcium absorption. But with high doses of vitamin D3, which is now often recommended, more calcium is absorbed, so it is important not to take too many calcium supplements. They can also interfere with iron and zinc absorption and when more than 2600 mg of calcium is taken magnesium absorption is inhibited as well. Calcium can interfere with thyroid hormone supplements (take 4 hours apart) and may reduce the effect of calcium channel blockers, drugs used for angina or high blood pressure.  There is a balance between calcium stored in bone (99% of total body calcium) and the circulating portion of 1% of calcium in the blood. The parathyroid hormone and calcitonin are also involved in this balance. Hypercalcemia is the condition when calcium is too high. Common causes are the improper use of diuretics (thiazide diuretics), overuse of calcium carbonate supplementation (often for osteoporosis) and overuse of vitamin D3, which increases the absorption of calcium (Ref.3). See your family doctor for blood tests and advice what to do in your case.

4. High protein diets and protein (amino acid) supplements:

Many protein supplements are available through health food stores and vitamin stores. The advertisers often state that our food would be substandard and these supplements would help “to regain strength”.  Athletes hope to get stronger muscles from amino acid supplements because they are the building block for protein that builds up muscles. Fact is that no supplements are needed when you eat balanced meals containing meat and fish and you exercise regularly. The protein in your food will be broken down into amino acids and your body metabolizes this into your own protein. Here is a website that reviews the subject of supplementation with amino acids.

It is clear from this that this is a rather complex problem. Vegetarians may require these supplements to replace protein for the missing meat intake. But the rest of us have to guard ourselves against overdosing with too much meat, amino acids supplements or protein supplements.

High protein diets (Atkins diet and others) have been glorified as being helpful for weight loss. But the long-term effect of such diets lead to chronic kidney damage in those with diabetes and high blood pressure as evidenced by protein leakage in the urine (called ”microalbuminuria”, Ref.4).

According to this reference the average protein requirement is 0.6 g of protein/kg body weight/day. This text comments that this would be compatible with the World Health Organization (WHO) recommendation for protein intake. For a person weighing 140 lbs. this translates into about 50 grams of protein per day. Here is a website that explains the upper limit of meat intake with the example of an 8-ounce portion of top sirloin steak.

Protein supplements have become very popular, but you need to be careful when you supplement with this that you do not get an overdose of amino acids. Amino acid profiling has been useful for physicians and naturopaths to examine deficiencies in children or adults checking for essential amino acids in the blood.  However, in the industrialized countries such as the US, Canada and others the larger concern is now the overuse of meat in our food (e.g. Atkins-like diets) and protein supplements. The same amino acid screening tests will find several of the ingredients (amino acids) in these protein supplements to be too high. In this case it is imperative to stop the protein supplements to prevent amino acid toxicity.

This study warns that not enough is known how performance-enhancing supplements affect the metabolism of the body. There are discussions that perhaps upper limits for amino acid supplements need to be established:

5. Creatine supplementation:

Other supplements of concern are creatine supplementation in the sports-minded and in athletes who want to build up muscle mass. Creatine is synthesized by the liver form amino acids derived from fish and meat that is broken down into the amino acids arginine, glycine and methionine. So, there is no shortage, but athletes and sports minded people want to push the envelope and take in additional creatine that helps their energy metabolism (ATP production) in the muscles to increase their performance (Ref. 5) Creatine is vital for the brain, the heart, the kidneys and the eyes (retina). It is a buffer for lactic acid during anaerobic exercise. Some of the side effects are muscle cramps, diarrhea, fluid retention and kidney failure when exposed to high heat and dehydration. There are no long-term studies of the use of creatine supplements, yet some athletes are taking them long-term.

Conclusion:

We are tempted by various merchants and infomercials to take in more and more vitamins and supplements including protein and amino acid supplements. But when you eat well-balanced meals, preferably organic food, you already have enough protein, nutrients, calcium, vitamin C and vitamin A contained in food. So you may be inadvertently putting a strain on your kidneys that have to eliminate whatever it is that is too much for your body to take. Your liver may also be quietly working overtime as well. Your brain gets overactive by the surplus of amino acids that are utilized by the brain to make brain hormones. Your system can only take so much; at one point a surplus of supplements will make you sick! So, be vigilant and think about what your regular food intake already provides. Do you really need that supplement or do you already get enough from your food intake? Are you falling for some marketing scheme? Remember, you are the steward of your own health!

References:

1.Shannon: Chapter 69: The Vitamins. Haddad and Winchester’s Clinical Management of Poisoning and Drug Overdose, 4th ed.© 2007 Saunders

2. Mandell: “Water-Soluble Vitamins”. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 7th ed. © 2009 Churchill Livingstone

3. Rakel: Chapter “Disturbances in Calcium and Phosphate” and chapter entitled “Vitamins and Minerals”. Textbook of Family Medicine, 8th ed. © 2011 Saunders

4. “High Dietary Protein Intake” in “Taal: Brenner and Rector’s The Kidney”, 9th ed. © 2011 Saunders

5. DeLee: DeLee and Drez’s Orthopaedic Sports Medicine, 3rd ed. © 2009 Saunders

Last edited April 30, 2014

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Mar
08
2014

Protecting Yourself From Environmental Toxins

Environmental toxins are toxins that may be in your drinking water, in what you eat, in the air you breathe, or they enter your body through your skin when you swim in contaminated water or walk on a sandy, wet beach.

In the following blog I will address some of these issues and how we can defend ourselves against toxins.

The youngest and most vulnerable

Toxins are particularly bad for infants and premature babies.

The reasons for this are the following ones: their kidney function (tubular secretion) is only 20% to 30% of that of an adult; the cytochrome P-450 enzyme system in the liver, one of the toxin eliminators is slowed down to only 25% to 50% of the adult activity and glucuronidation in the liver, another detoxification process, reaches adult levels only at the age of 3 years. The kidneys and the liver are limiting the removal of toxins by way of urine and bile in the newborn. Stomach acidity in a premature has a pH of 4.7, in a full-term newborn 2.3–3.6 and in an adult 1.4–2.0. This is important to note as a lack of stomach acid increases susceptibility of newborns and infants to gastrointestinal infections and cause diarrhea. Percutaneous absorption in newborns is much higher than in adults, which makes them very susceptible to absorbing toxins through the skin (Ref.1).

Diabetes from environmental toxins

Environmental toxins can cause insulin resistance and type 2 diabetes.

Bisphenol A (BPA) is used to make polycarbonate and epoxy resins and is found primarily in food and beverage containers. The world population has been exposed to this since 1957 and as a result 90% of US residents have detectable levels of BPA in their urine. Ref.2 explains that the higher the urine concentration of BPA, the higher the risk is for developing diabetes.

Persistent organic pollutants are another source of concern: pesticides and herbicides, dioxins, polychlorinated biphenyls, hexachlorobenzene, and hexachlorocyclohexane have all been found in humans. Several investigators have shown that virtually all of the risk in obese patients to develop diabetes comes from the fat-soluble persistent organic pollutants (Ref.2).

Inorganic arsenic is another pollutant that is found in soil and rock naturally and finds its way into the drinking water. About 8% of the public water system of the US exceeds 10 mcg/L for drinking water, which has been set as the safe limit for drinking water by the US Environmental Protection Agency’s standard. Anything above those levels is considered toxic.Ref.2 describes that people who ingest inorganic arsenic will excrete it in the urine; the highest group with arsenic in their urine had a risk of 3.58-fold to develop diabetes when compared to the lowest group. Curiously enough organic arsenic that is found in fish and shellfish is excreted in the urine unchanged and does not cause diabetes. Overall this indicates to me that nobody should consume or cook with contaminated water that contains inorganic arsenic. Reverse osmosis filters will protect you from this risk.

Protecting Yourself From Environmental Toxins

Protecting Yourself From Environmental Toxins

Other toxins around the house

Volatile organic compounds are often contained in carpets, but also in laser and inkjet printers. They are part of everyone’s life as this link shows. Varied symptoms like irritation of eyes, nose or throat, breathing problems, headaches, loss of coordination, damage to the liver, kidneys and the brain have been reported after exposure to volatile organic compounds. Long-term exposure can even cause cancer in animals and has been suspected to cause cancer in humans as well.

Air fresheners and cleaning solutions that contain ethylene-based glycol ethers and terpenes have been the subject of a study that examined concentrations in the air and interaction with ozone that can also be released by some cleaners. As this link shows the investigators concluded that with exposure to high enough concentrations and long enough exposures to these fumes lung cancer can be caused in cleaning personnel. They recommended to use cleaning solutions only in diluted form and to air out the premises well after cleaning. Another component of many air fresheners and cleaning chemicals is paradichlorobenzene, the same chemical that is contained in mothballs.

There have been problems with flame retardants: polybrominated diphenyl ethers, which are cancer producing; they have been outlawed in the US since 2004, but older mattresses, upholstery, television, computer casings and circuit boards may still contain them.

Lead and mercury poisoning, and radioactive pollutants

Manufacturers were not allowed to use lead in paints anymore since 1978. Paint from buildings older than that still may contain lead. There have been serious lead poisonings in children who were gnawing on items painted with lead containing paint. Lead causes problems with your central nervous system, brain, blood cells and kidneys. Just last year a news story about lead found in fashion jewelry surfaced warning about cheap fashion jewelry from China. Lead form these items can be absorbed through the skin and cause lead poisoning. Because of the apparent lack of regulations in China it is my recommendation not to buy anything that goes into your mouth or on your skin, if it has been grown or produced in China.

Mercury from tuna and other predator fish: It is sad that the oceans are polluted to the point where it has become unsafe to eat predator fish as there is an accumulation of mercury through the food chain.

How did things develop this way? Back 100 years and more ago gold panning and the purification process of gold caused mercury to enter into rivers and allow mercury to end up in the oceans where it has since accumulated; it just sits there as it has nowhere to go.

Coal burning (yes, there is mercury in coal) has also contributed to this by smoke being emitted from smoke stacks containing mercury vapors, which ended up returning to earth as polluted rain and drained through the river system into the oceans.

It is monomethylmercury that accumulates in the tissue of humans. It affects many organs, such as the brain, kidneys, lungs, and skin. It causes various symptoms like red cheeks, fingers, and toes; there can be bleeding from the mouth and ears; it can cause rapid heartbeats, high blood pressure, intense sweating, loss of hair, teeth, and nails. It also can cause blindness, loss of hearing, impaired memory, and lack of coordination, disturbed speech and birth defects. You may think all mercury comes from the outside. However, silver amalgam fillings in your teeth could also be the source of mercury poisoning. It is a good idea to replace amalgam/mercury fillings with ceramic fillings.

There are many forms of other marine pollution as this link shows.

One particular concerning aspect is pollution with radioactive materials as the Fukushima disaster in Japan has shown. Following the catastrophe on March 11, 2011 there have been several leaks of radioactive material into the ocean, which are described here. Dr. John Apsley II pointed out that with the explosions in Fukushima there were also several releases of radioactive pollution into the stratosphere. This pollution has subsequently traveled around the globe and has come down as radioactive rain. He has made it his ambition to help people minimize radiation exposure from nuclear accidents such as Fukushima.

Protecting yourself from toxins

Having said that pollution and toxins are problems that we are living with, how can we protect ourselves from all of that?

1. Avoid as many unsafe chemicals around you as you can. This includes checking ingredients in hair care and body care products, toothpaste, hair dyes, cosmetics, mouthwashes and underarm deodorants.  I have written a blog about toxins in the bathroom and what you should watch for.

2. I would recommend you switch from a standard food to organic food. It has become unsafe to eat non-organic meats, leafy vegetables, vegetables and fruit. There are too many residues of herbicides and pesticides contained also in meat, not only in vegetables and fruit. Washing will not remove these substances, even though some merchants may tell you otherwise. Buyer beware!

3. Detoxification methods are available and I have reviewed them in this blog. Briefly, to remove lead and mercury a formal intravenous chelation protocol should be followed.  Depending on how many heavy metal toxins you have on board, you may need only a few treatments or else up to 20. Here is a more conservative website stating that it would be safe to have silver amalgam fillings. I think that gold and ceramic fillings are much safer.

4. Genetically modified food is another danger as I have summarized in this blog. This is another reason why I like to stick to organic food. There is evidence that GMO food causes autoimmune diseases, infertility and chronic inflammation that can eventually lead to cancer. It may take decades to prove this, but I am not willing to be a human guinea pig.

5. I have mentioned in a prior blog that we live in a toxic world. You need to carefully look at your home and remove toxins. You need to assess your drinking water. A water analysis can tell you how good the water in your home is and whether there are concerns about inorganic arsenic. Usually places that sell filter systems can advise you in that regard. Your drinking water should either be bottled pure water or else reverse osmosis water that can be part of a filter system in your house.

6.Vitamins and supplements have been shown to support your cell integrity and have anti-inflammatory and antioxidant effects that protect you from toxins. I discussed this in detail in my NetHealthBook under nutrition. For instance vitamin D3 in doses of 5000 IU or more and CoQ-10 are powerful anti-inflammatories and CoQ-10 is also an antioxidant and preserves mitochondrial function. High fish oil supplements (3 to 6 Grams per day) have anti-inflammatory effects and protect your cell membrane integrity. With these overlapping qualities of vitamins and supplements your body will be in a much stronger position to defend itself against the negative effects of toxins. When you take multivitamins, this translates into telomere lengthening of 5.1% (or converted into a survival advantage of 9.8 years when it is accumulated over a life time). Ref. 4 explains this in more detail.

7. Exposure to radioactive substances is a scary thought, but this is becoming more and more a reality, at least for those who live close to disaster areas such as the Fukushima site in Japan or the Chernobyl site in the Ukraine. But according to Dr. Apsley II low dose radiation that we have already received in the US and in Canada following the Fukushima disaster is equally disastrous (Ref.3). Many of the vitamins and supplements I have mentioned are also cell and mitochondria protective and will help with DNA repair following radiation damage, but you must avoid sugar and other refined carbs and starches to reduce the oxidative effect on cells and on LDL cholesterol to prevent premature aging and cell death. Ref. 3 contains a lot more detail about this and explains what specific supplements can be taken to detoxify your system from specific radioactive elements that function as free radicals. There are specific antidotes for radioactive iodine-129 and iodine-131, radioactive cesium-137 and others.

Conclusion

Many people shrug their shoulders when they hear that pollution has an effect on their lives. They feel that they are powerless and cannot do anything about this. The truth is far from this! Above I mentioned seven points that you can follow to counter toxins. On top of that you can get politically active and urge your government representative to create a nuclear free zone in your area. Ref. 3 contains compelling evidence why this is so important not only for us now, but for future generations and the future of mankind. We need to hold those who provide us with food and beverages accountable for the quality of these. Shrugging it off is not good enough. Get involved. Buy organic food. Avoid the section in the grocery store where sugar and high carb foods are sold. It’s good for your own health, but it will collectively change the mentality of the grocery store owners who will notice that they are stuck with the comfort foods that sold well in the past. This new trend will result in cheaper prices for healthy foods and more availability of organic food.

References

1. Shannon: Haddad and Winchester’s Clinical Management of Poisoning and Drug Overdose, 4th ed. © 2007 Saunders. Chapter 18:“Toxicologic Issues in the Neonate”.

2. Rakel: Integrative Medicine, 3rd ed. © 2012 Saunders. Chapter 31: “Insulin Resistance and the Metabolic Syndrome”.

3. Dr. John W. Apsley II : “Fukushima Meltdown & Modern Radiation: Protecting Ourselves and Our Future Generations” © 2011. Temet Nosce Publications, Sammamish, WA 98075

4. Xu, Qun, Parks, C.G., DeRoo, L.A., Cawthon, R.M., Sandler, D.P. and Chen, H. Multivitamin use and telomere length in women. American Journal of Clinical Nutrition 89 (April 2009):1857-63. Full text (PDF): http://ajcn.nutrition.org/content/89/6/1857.full?sid=9aab0e13-b4d2-42ad-b44c-15cffc6771c3

Last edited March 8, 2014

Feb
01
2014

Early Alcohol Use Will Result In Memory Loss Later In Life

Researchers found that heavy alcohol use in males during midlife paves the way to memory loss from dementia later in life.

I thought that this would be a good topic to review the effect of alcohol in general. Alcohol is a known cell poison, yet cardiologists keep on referring to the beneficial effects of that 1 glass of wine per day that will prolong your life. I will attempt to explain these diverse effects, where small amounts are supposed to be good for you while high amounts can be very damaging.

Review of the effects of alcohol

50% of the world population drinks alcohol, 10% to 20% have chronic alcoholism (Ref.1).  Just recently a Guardian news study was released showing that an astounding 25% of Russian men die before reaching the age of 55, compared to only 7% of men in the United kingdom and less than 1% of men in the US. The study looked at the effects of consuming large amounts of vodka.  There are about 10 million chronic alcoholics in the US. Chronic alcohol consumption leads to 100,000 deaths every year in the US. More than 50% of these deaths are from traffic accidents, the rest from medical problems caused by alcohol (Ref.1). Most of the alcohol gets detoxified through the liver cells and is metabolized into acetaldehyde. This involves the cytochrome P-450 system. That means that when a person also takes narcotics, sedatives or psychoactive drugs that are also metabolized through this liver enzyme system drugs and alcohol are taking much longer to be metabolized. This can lead to lethal overdoses that we hear about on TV all the time, hence the warning that you must not mix alcohol with drugs.

Early Alcohol Use Will Result In Memory Loss Later In Life

Early Alcohol Use Will Result In Memory Loss Later In Life

Alcohol is a cell and nerve poison. The most vulnerable organs in the body are the liver, brain, heart, pancreas, bone marrow and stomach. So, here are a number of conditions caused by drinking alcohol:

a)    Anemia: When a person drinks heavily and regularly anemia shows up in a blood test. Alcohol has a toxic effect on the bone marrow, which interferes with the production of red blood cells. But certain vitamins required by the bone marrow to manufacture red blood cells are often also missing in the diet of an alcoholic, which contributes to anemia as well.

b)    Cirrhosis of the liver develops in 10% to 20% of heavy drinkers. With cirrhosis part of the liver cells get replaced by fibrotic tissue and in advanced cases this can lead to a hepatic coma and death. Others are developing alcoholic hepatitis. This is an inflammation of the liver with fever and jaundice where the skin and eyeballs turn yellow. It is associated with severe abdominal pain.

c)    Gastritis: Alcoholic gastritis is common, but often undetected. The affected individual may just have stomach pains for a few days, or vomit food and/or blood in addition. With continued use of alcohol it may turn chronic. Alcoholic gastritis can turn into gastric ulcers with massive bleeding that often lead to death.

d)    Pancreatitis: The pancreas is a particularly vulnerable glandular tissue, which gets damaged by regular alcohol intake and with chronic alcohol intake gets partially replaced by fibrotic tissue causing the feared and painful chronic pancreatitis. This is a condition with vomiting and severe abdominal pains that can be unrelenting.

e)    High blood pressure, seizures, dementia, depression, heart irregularities and nerve damage:

You may ask yourself how all of these conditions would be reasonably under one heading. The heading for this is “nerve damage”. Let me explain: The sympathetic nerve is very sensitive to alcohol toxicity and when the sympathetic nerve fibers are damaged, you will develop high blood pressure. You see your physician, get blood pressure medication, but the pressure is difficult to control, if you continue to drink alcoholic beverages. It does not make sense to just add blood pressure pills and hope that this will cure your problem. Seizures are due to direct nerve damage in the more sensitive parts of the brain, which will cause these areas to produce extra electrical activities, which we call seizures. Again, just treating with anti-seizure medications is not the solution. Avoidance of alcohol is the other part of the treatment schedule. Dementia from heavy alcohol use is due to direct nerve atrophy in the brain. Our brain shrinks normally 1.9% to 2.8% per decade, depending on which research papers you read. But in the presence of heavy drinking the frontal lobe of the brain is particularly vulnerable to brain shrinkage.

As this publication shows, mild and moderate drinkers did not suffer more frontal lobe shrinkage than abstainers, but heavy drinkers had a 1.8-fold higher risk of frontal lobe shrinkage on average when compared to abstainers. It was calculated that alcohol had contributed 11.3% to that frontal lobe shrinkage.

The rest of the toxic effect on the nerve tissue explains why depression would develop. The frontal brain contains most of the serotonin producing nerve cells. When serotonin-producing nerve fibers get damaged, the body does not produce enough serotonin to prevent depression from setting in; GABA producing cells often also get damaged, which causes anxiety. It’s not good enough to just prescribe anxiolytic drugs to which the patient will get addicted. The whole person needs to be treated, and abstinence from alcohol has to be part of the program.

Heart irregularities (atrial fibrillation, ventricular fibrillation) can be life-threatening complications due to the toxic effect of alcohol on the nerve fibers within the heart muscle. Emergency physicians are aware of the connection of these conditions to alcohol consumption. Some people’s hearts are more sensitive to the effects of alcohol than others. The most common cause of temporary atrial fibrillation is excessive alcohol intake (holiday heart) according to Ref. 2.

Finally there is the effect of alcohol on nerves in the body. This explains that heavy alcohol consumers can come down with painful pins-and-needles sensations in their hands and feet or with numbness or loss of muscle strength. When the parasympathetic nervous system is affected embarrassing incontinence or constipation can result. Erectile dysfunction in men is also very common. Viagra and continuing to drink is not the solution.

f)      Gout: This painful formation of uric acid crystals in joints can be precipitated in sensitive individuals by consuming alcohol in combination with eating large helpings of beef. There may be a history of gout in the family. Treatment for this is to refrain from alcohol and avoid foods that are leading to uric acid production when ingested.

g)    Cancer: When the body detoxifies alcohol in the liver, the breakdown product is acetaldehyde, which is a known cancer producing substance. A whole array of cancers are known, which come from heavy, chronic alcohol consumption: cancers in the mouth, larynx, esophagus, stomach, pancreas, liver and colorectal cancer have all been linked to excessive alcohol intake.

h)    Cardiovascular disease: heart attacks and strokes can be caused particularly by binging; it is thought that binging makes platelets from the blood more sticky so they clump together and cause blood clots, which in turn leads to heart attacks and strokes.

i)      Infections: Alcohol weakens the immune system, which is another effect on the bone marrow similar to causing anemia, except that this is the toxic effect on the white blood cells and lymphocytes. Heavy alcohol consumers are more prone to pneumonia, to HIV, sexually transmitted diseases, and tuberculosis.

Cardiology view of preventative alcohol

Despite all of these hair raising toxic effects cardiologists have painted the rosy picture that 1 glass of wine for women and 2 glasses of wine for men per day will prevent heart disease. What is the true story here?

Ref.2 points out that there are about 100 prospective studies that confirm that there is an inverse relationship between mild to moderate alcohol consumption and “heart attack, ischemic stroke, peripheral vascular disease, sudden cardiac death, and death from all cardiovascular causes”. It describes further that the reduction of risk in these various studies was persistent and consisted of a 20% to 45% risk reduction. Using blood tests investigators have found that this is because of an increase of HDL cholesterol, reducing blood clotting, making platelets less sticky and reducing inflammation as evidenced by a reduction of the C-reactive protein. Further research has pinpointed that it is the phenols and resveratrol that are contained in alcoholic beverages that are responsible for the beneficial effects. The bad news is that three glasses of wine or more do the opposite, so does binge drinking. Unless you are extremely disciplined and never increase your allowed limit (1 drink for women, 2 drinks for men) you will CAUSE heart disease rather than PREVENT it (Ref.2). Some people have a family history of breast cancer or colon cancer and they should avoid alcohol altogether; also people coming from alcoholic families should avoid alcohol.

Conclusion

Where does this leave us with regard to prevention of heart attacks, strokes and hardening of the arteries in the legs (peripheral vascular disease)? If you are disciplined and stick to the limits, you could prevent 20% to 45% of cardiovascular risk. The brain study mentioned in the beginning of the blog would also confirm that there was no difference between dementia or brain shrinkage when mild to moderate drinkers were compared to abstainers over 10 years. What is not told by the wine industry is that the same effects that prevent cardiovascular disease in mild to moderate drinkers can also be achieved by natural means: exercising regularly will raise your protective HDL cholesterol; taking ginkgo biloba, flax seed and omega-3 fatty acids thins your blood and the platelets are getting less sticky; omega-3 reduces inflammation and resveratrol elongates telomeres making you live longer. At the A4M conference in Las Vegas in December 2011 there were three speakers who pointed out that even small amounts of alcohol will poison mitochondria of your cells and interfere with normal hormone action. This was enough to make me join those who abstain alcohol completely. One thing has not yet been investigated in long-term studies, namely how small effects of alcohol may affect the body over several decades and over an entire lifetime. Despite all the promises of interest groups that red wine is a trendy drink for those interested in heart health, the fundamental long-term studies are missing. What does a guy do with a healthy heart and a brain that is not functioning too well? I just do not want to be the guinea pig in that worldwide study.

More information on alcoholism: http://nethealthbook.com/drug-addiction/alcoholism/

References:

  1. Kumar: Robbins and Cotran: Pathologic Basis of Disease, Professional Edition, 8th ed. © 2009 Saunders
  2. Bonow: Braunwald’s Heart Disease – A Textbook of Cardiovascular Medicine, 9th ed. © 2011 Saunders

Last edited Nov. 7, 2014

Jan
18
2014

The Super Powers Of Vitamin D

Originally, when vitamin D was found to be the missing ingredient in preventing rickets in growing children the recommended daily allowance (RDA) to prevent rickets was found to be 400 IU of vitamin D. The active metabolite has been identified as vitamin D3 for which the body has receptors on all vital organs (heart, brain, bones, kidneys, liver). In recent years new insights have been gained as it turns out that the RDA’s were set much too low for many diseases that can develop when vitamin D intake is too low, particularly in the aging population. Higher doses of vitamin D3 in the range of 800 to 1000 IU per day have been shown to prevent osteoporosis, falls and fractures in older adults and in nursing home populations. But the immune system of everybody is dependent on higher doses of vitamin D3. Recently (Dec. 12 to 15, 2013) I attended a lecture at the A4M conference in Las Vegas where Dr. Eisenstein reviewed the latest on vitamin D3. It is now known that 2/3 of the US population is deficient for vitamin D as measured by blood tests (less than 25 ng/ml).  The standard test is the 25-hydroxy-vitamin D level (abbreviated as 25(OH)D level). It is now known that you require at least a level of more than 40 to 60 ng/ml of 25(OH)D as measured in the US, which translates to more than 100 to 150 nmol/L measured in metric units in other countries, to prevent cancer.

The Super Powers Of Vitamin D

The Super Powers Of Vitamin D

Metabolism of vitamin D3

90% of the vitamin D3 that we need comes from exposure to sunlight, which transforms a cholesterol metabolite (7-dehydrocholesterol) into the vitamin D precursor (vitamin D3 or cholecalciferol). This is what we absorb from naturally occurring fish oil and oily fish, but otherwise this does not naturally occur in foodstuffs (Ref. 1). Dr. Eisenstein pointed out that it is well known that people living north of the 37th degree latitude lack vitamin D3 because of a lack of sun exposure, particularly in the winter season. People south of the 37th degree latitude have enough sun exposure, but wherever you live, it is advisable to have your vitamin D3 level measured (as 25(OH)D level). If you do not eat enough fish or fish oil, the levels likely are too low as is the case for 2/3 of the US population. Vitamin D3 supplements will have to be taken by those whose levels are too low. Vitamin D3 is further metabolized by the liver and then by the kidneys into the active vitamin D compound, called 1,25(OH)2D3 (which is called “calcitriol”). The main effect of calcitriol is to absorb calcium and phosphate from the intestine into the blood stream. Together with vitamin K2 as explained in a prior blog these minerals are then taken up by the bone to prevent osteoporosis or rickets in the growing child. What has not been known for a long time is that vitamin D3 is also necessary for normal cell metabolism by most of your body cells, but particularly by the vital organs like the brain, the heart, the kidneys, the liver, the immune system and the bone. However, doses of 5000 IU to 10,000 IU of vitamin D3 capsules per day are required for optimal vitamin D3 health. This will lead to levels of below 200 ng/ml of 25(OH)D levels, which have been proven to be safe. According to Dr. Eisenstein no toxicity has been found below 30,000 IU of vitamin D3 per day, but based on other authors a dose of 10,000IU should be adequate for most people. Strangely enough colored people also have to take vitamin D3 supplements as their the higher melanin pigment in the skin filters out UV light so effectively that their 25(OH)D level can be low. Always err on the cautious side and have your vitamin D3 blood level taken.

Vitamin D3 has a characteristic stereotactic configuration (cis-triene structure), which allows it to bind free radicals and function as an antioxidant (Ref.2).

What are some of the clinical effects of vitamin D3?

1. Vitamin D3 has diverse effects on organs systems as Dr. Eisenstein summarized: vitamin D3 lifts depression and has been found to be of particular value for drug resistant depression. Take 5000 to 10,000 IU of vitamin D3 per day.

2. Muscle power increases with vitamin D3, particularly in those who work out regularly.

3. Many fertility clinics pay attention to vitamin D3 levels, as the higher the blood levels of vitamin D3 in a man, the faster this sperms move! And the more vitamin D3 she has on board, the better she ovulates. The end result is a higher pregnancy success rate when both partners take 5000 to 10,000 IU of vitamin D3 per day

4. Also, if a woman takes vitamin D3 during her pregnancy, the first set of teeth in the offspring will have fewer cavities.

5. Brain development in autistic children is much improved with vitamin D3 in higher doses. This needs to be combined with detoxification methods and supervised by one of the DAN physicians.

6.Chronic pain typically improves when vitamin D3 deficiency, which almost always is present in patients with chronic pain, is treated with vitamin D3 supplementation.

7. To prevent flus and colds and other infectious diseases, take higher doses of vitamin D3. When you come down with a flu, it is safe to increase your daily vitamin D3 intake to 30,000 IU of vitamin D3 for a few days until your symptoms improve, then resume your maintenance dose of 5000 IU to 10,000 IU per day.  This year’s dominant flu is the type A, subtype H1N1 – also known as the swine flu. Children should get 50% of the dose regimen detailed for adults when they develop a flu (for children: 15,000IU for three to five days , with tapering to a maintenance dose of 2500 to 5000 IU until blood levels of 25(OH)D are available). Here is a website of Dr. Cannell where he discusses dosages as well.

8. Asthmatic patients do better with vitamin D3 supplements requiring less maintenance anti-asthmatic medicine to keep them balanced with regard to their airways.

9. Chronic low vitamin D3 levels cause brain damage including Alzheimer’s disease. In this context it is important to know that the enzymatic conversion in the liver and kidneys slow down as we age requiring higher doses in older patients. This may have been the reason for the confusion about relatively low doses of 400 IU of vitamin D3 preventing rickets in children versus the need of vitamin D3 in middle aged and older patients where much higher doses are required as already explained.

10. High blood pressure is linked to vitamin D3 deficiency and it is better manageable with medication when vitamin D3 levels are normalized.

11. Live longer with vitamin D3. How is this possible, you might ask: the answer has been found in the telomeres, the shoelace like structures at the end of the DNA strand of each cell. Vitamin D3 lengthens the telomeres and promotes telomere repair; this is associated with a longer life span. Centenarians have longer telomeres. You can measure telomere length, but it is a pricey test, which is not for everyone, contrary to supplementation with vitamin D3 that should be taken by everyone!

12. As already indicated, vitamin D3 strengthens the immune system, but it also modulates the inflammatory response from muscle damage, so athletes can perform better. Patients with multiple sclerosis will improve as it slows down the inflammatory process. But other inflammatory diseases like arthritis, inflammatory bowel disease and even cancer will respond favorably to higher doses of vitamin D3 (20,000 to 30,000 IU of vitamin D3 in these cases). This is information that has not yet percolated into mainstream medicine, but will do so in the next few years (or decades?).

13. Higher percentages of cardiovascular disease are found in patients who have lower than 15 ng/ml  25-Hydroxy- vitamin D3 levels in their blood meaning that vitamin D3 supplementation prevents heart disease (Ref.3).

What are toxic vitamin D levels?

What is known about the safety of vitamin D3, particularly the higher vitamin D3 doses? First, it is wise to have your 25(OH)D blood levels taken from time to time. If any of these levels exceed 200 ng/ml it would be prudent to reduce the vitamin D dose or stop supplementation for a while. Otherwise it has been difficult to establish a toxic range.

This website claims that 40,000 IU of vitamin D3 or more would lead to toxic levels where the blood calcium levels would be increased, which can be measured as hypercalcemia. However, another study done in 2007 showed in MS patients that took 40,000 IU per day and that led to a blood level of 400 ng/ml of 25(OH)D did not lead to increased calcium levels and did not lead to hypercalciuria (too much calcium in the urine). So, all of the papers that either indicated to the public that it would be unsafe or unnecessary to take vitamin D3 seem to have other agendas than communicating the truth. Had it been true that calcium would be released from the bones or calcium were absorbed too much from the gut, this would have caused calcification of the bones, soft tissues, heart and kidneys. Also, kidney stones would have developed. However, a low calcium diet combined with corticosteroid drugs usually leads to a full recovery within a month. Interesting that all of the dire predictions regarding toxic vitamin D3 levels did not materialize. Here is another website discussing vitamin D3 dosing.

I talked to a participant of the conference (who has a fellowship degree of the A4M) about what is really known about vitamin D3 toxicity. He told me that there has been an unintentional overdose where a compounding pharmacy made a mistake, so that a patient accidentally received a dosage of 500,000 Units of vitamin D3 per day for a full three months, before the mistake was uncovered. The patient felt sluggish, but did not have any other symptoms. He was told to stop the vitamin D3 compound. He had an uneventful recovery with no detrimental effects. At this point no overdose of vitamin D3 has been established.

Conclusion

Vitamin D3 is a vital supplement that has been shown to prevent not only rickets in children, but also depression, MS, infections and even many cancers (Ref. 4). As usual there will be many critiques that doubt the validity of the above statements. But I have found that all of these effects described above were confirmed in several sources of various medical information. Keep in mind that negative rumours have a tendency to linger on for years.

More information on vitamin D3 for prevention of osteoporosis and hardening of arteries: http://www.askdrray.com/calcium-vitamin-d3-and-vitamin-k2-needed-for-bone-health/

Vitamin D3 deficiency can cause pancreatic cancer: http://nethealthbook.com/news/insufficient-vitamin-d3-linked-to-pancreatic-cancer/

References

1. McPherson: Henry’s Clinical Diagnosis and Management by Laboratory Methods, 22nd ed.,  © 2011 Saunders

2. Rheumatic Diseases Clinics of North America – Volume 38, Issue 1 (February 2012) , © 2012 W. B. Saunders Company

3. Wang TJ, Pencina MJ, Booth SL, et al:  Vitamin D deficiency and risk of  cardiovascular disease.   Circulation 117. (4): 503-511.2008.

4. “Recognition and Management of Vitamin D Deficiency”: American Family Physician – Volume 80, Issue 8 (October 2009),  © 2009 American Academy of Family Physicians

Last edited Nov. 7, 2014

Jan
04
2014

Impressions From The 21st Annual World Congress On Anti-Aging Medicine (A4M) In Las Vegas

Every year in mid December Vegas hosts the world A4M conference (from the American Academy Of Anti-Aging Medicine). This year’s conference was at the Venetian/Palazzo Resort in Las Vegas, NV from December 13th to 15th, 2013.

There were more than 3,500 attendees who participated in this yearly continuing medical education event in preventive and integrative medicine. Over 50 speakers reviewed various anti-aging topics including aesthetic medicine and stem cell topics. In addition there was a huge exhibition with over 300 exhibiting companies of health related products and books.

I attended this conference to see what is new in anti-aging medicine, which is the focus of my interest since my retirement in 2010.

Here are some highlights the way I saw it. As the topics were varied, I simply present a potpourri of snippets, all of which have some usefulness.

1. Opening remarks by Dr. Ronald Klatz and Dr. Robert Goldman

Dr. Klatz pointed out that the A4M has been very active over the years in lobbying for making supplements more available to the public. In 1995 the A4M was defending melatonin as a harmless sleep aid and the FDA agreed to allow it to be freely sold in health food stores. In 1996 DHEA followed this trend. Because of pressure of the A4M on the FDA Co-Q10, an important cardio protective supplement became available in health food stores in 1998. In 1999 the A4M stated in a public statement that newer research has confirmed that insulin is involved in obesity and diabetes and is an important aging substance. Those who continue to have high fasting insulin levels, will age faster than the average population. But those who lose weight, and exercise will reduce fasting insulin and will no longer age prematurely. The reason for this is that inflammation is the cause of high blood pressure and of cardiovascular disease like heart attacks and strokes. Reduce or eliminate fasting insulin and you eliminate the risk for heart attacks and strokes. In 2004 the A4M announced that stem cells could be used as an important tool to treat various end stage diseases to allow people to live longer. Since then this has become a huge specialty area. There was also a separate pre-conference workshop on stem cells. In 2009 the A4M announced that vitamin D3 was effective beyond bone health. Every cell in the body contains vitamin D receptors. Originally the 400IU per day RDA dose was established to fight rickets. Now it is recognized that 4000 or 5000 IU of vitamin D3 are required every day for a multitude of normal body functions. People with the poorest lifestyles have the shortest life expectancy, 66.5 years in Native Americans of South Dakota; in contrast the longest life expectancy in the US is found in Asian American women in New Jersey with 91.8 years. It just so happens that in New Jersey most of the 26,000 A4M physicians are practicing, which may be one of the reasons for the impressive longevity figures.  Dr. Katz suggested that we should recommend the following website to people: http://www.worldhealth.net/  This is the official medical news website of the A4M and deals with the latest health recommendations.

Dr. Goldman added to this that the anti-aging industry is growing rapidly (0$ in 1991; 250 billion $ in 2012; an estimated 345 billion $ in 2018).

He also emphasized that anti-aging can only be achieved, if blood tests are done early to detect any hormone or chemical abnormalities in the beginning stages before permanent organ damage sets in. Only with early detection can effective anti-aging treatments be initiated. Prevention is always better than waiting for an emergency to occur and then wanting to fix it, as it is commonly done in the conventional medical system.

Impressions From The 21st Annual World Congress On Anti-Aging Medicine (A4M) In Las Vegas

Impressions From The 21st Annual World Congress On Anti-Aging Medicine (A4M) In Las Vegas

2. Hypertension diagnosis and treatment

Dr. Mark Houston (Nashville, TN) talked about new and revolutionary concepts in treating and diagnosing hypertension (high blood pressure). Endothelial and vascular muscle dysfunction are now in the center of the researchers’ attention. The reason for blood pressure to get elevated is from a combination of inflammation, oxidative stress and autoimmune dysfunction of the vascular system. Decades before the blood pressure shoots up, there are vascular and heart abnormalities. 24 hour ambulatory blood pressure monitoring (24hour ABM) is the most reliable test for assessing blood pressure.

Among other things a micronutrient test was suggested as this way a lack of magnesium could be detected. Too little magnesium in the blood has to be treated with magnesium citrate supplements.

In terms of treatment it was interesting to note that diuretics and beta-blockers are no longer recommended, because of serious side effects. Instead of these medications the treatment of choice now are calcium channel blockers (Diltiazem etc.) and angiotensin II receptor blockers (Losartan etc.):

3.  Testosterone therapy in men

This was the topic of Dr. Abraham Morgentaler, a professor of urology at Harvard Medical School. He asked whether it is a panacea, a scourge or the next big thing in medicine. He went through various literature citations that showed that there is no relationship between testosterone or DHT (de-hydro-testosterone) and prostate cancer. In a New England Journal of Medicine publication Dr. Morgentaler has shown by doing extensive prostate biopsies on men with or without prostate cancer that testosterone treatment did not cause prostate cancer or make prostate cancer worse. He found that testosterone treatment invariably made men feel better, and they had more energy using testosterone. They also lived longer. He also debunked a recent JAMA publication from November 2013 that stated testosterone replacement would have led to increased heart attacks. He explained that he called the editor after calculating the raw data and coming to the conclusion that the authors had miscalculated and misrepresented the data, as the risks of heart attacks in men using testosterone were actually half of what the controls without testosterone replacement showed. However, the editor elected to keep the false data in the publication, which has caused confusion with the public and with the medical profession. Here is another rebuttal by Dr. Trutt who came to the same conclusion. Fact is and this is in agreement with many other medical publications in the US, Europe and around the world that testosterone replacement (with bioidentical testosterone) in a testosterone deficient man will cut the risk for heart attacks and strokes into half of what it would be if he did not replace with testosterone. However, only bioidentical testosterone will show this heart and brain saving effect, as there is a key/lock mechanism between bioidentical testosterone and the testosterone receptors of heart and brain cells and the testosterone receptors in the arterial walls.

4. Keynote speaker

Suzanne Somers was the keynote speaker on the first day of the conference in a talk entitled “Our time has come”. Her books have greatly contributed to the popularity of the anti-aging movement in North America and around the world. She described how important it was for her to take charge of the health care in her own case and to explore alternatives to treat her breast cancer in the past. She allowed a lumpectomy, but she refused chemotherapy which conventional medicine wanted to force on her. Instead she changed her lifestyle completely as summarized in her books, particularly in “Breakthrough”. She also became one of the pioneers in the US to get the newly FDA approved mesenchymal stem cell/fat cell transplant done on the affected breast to restore the pre-surgical appearance. She made a plea to those who can afford it to bank their stem cells, which was later reiterated by Dr. Terry Grossman, MD whose lecture I did not review here. I noted this key sentence in Suzanne Somers’ speech towards the end: “I work prophylactically to take care of my health”. How often have I wished in the past that every one of my patients would have this attitude!

5. Hormone testing and nutrition

Jim LaValle, an adjunct professor in the College of Pharmacy, University of Cincinnati has more than 27 years of clinical experience in the field of natural therapeutics and functional medicine. He mentioned that many people are toxic from a leaky gut due to faulty nutrition, which in turn will lead to heart disease and kidney disease. Once a patient has heart failure, a leaky gut will make the heart failure worse. Leaky gut leads to multiple autoantibodies, which causes various autoimmune diseases. Another area he concentrated on in his talk is the fact that neuroplasticity in the brain can restore people’s brain after brain injuries or when autoimmune diseases have attacked the brain. Through lifestyle changes stem cells in the support tissue of the brain, called glia cells, can develop into neural progenitor cells, immature newborn granulocyte cells and eventually into mature nerve cells. In other words the same sequence that occurs in the embryo with brain maturation can also occur in adults. Researchers are only learning now how to approach this difficult subject. He pointed out that there has to be a balance between the gut, the brain and the immune system. As the gut is also an immune organ (Peyer’s patches) where Th1, Th2 and Th17 lymphocytes are produced, it is important to manage your gut through probiotics and through intake of organic foods to get away from anything that disbalances the gut/immune system/brain interaction. At the end he briefly touched on two important facts: zinc is a trace element that is important for prevention of a leaky gut as it keeps the cell bridges of the lining of the gut intact. However, when zinc levels are done on patients in the hospital setting, he found that patients are often deficient for zinc, but they are responding very rapidly to zinc supplementation. Stress, which causes high cortisol levels leads to lowered endurance, autoantibodies and allergies. By checking other hormones, which need to be in balance with cortisol the caregiver can recognize what is wrong with a patient and help restore the hormone balance with bioidentical hormones. This will also take care of the leaky gut, the autoimmune diseases and improve asthma in a person who has allergies.

6. Aging and the short telomere connection

William Andrews, PhD has worked in the biotech industry for 28 years and had obtained his Ph.D. in Molecular and Population Genetics at the University of Georgia in 1981. In the last 15 years he has focused on finding ways to extend the human lifespan by interfering with telomere shortening in human cells. He shared some interesting facts with the audience: reproductive cells do not age and their telomeres stay long. He said that in order to age gracefully it helps to know the length of your body’s telomeres. He recommended using the HT Q-Fish telomere test, which is a genetic test that gives an average of the telomere status of your body. This test will determine the %-age of short telomeres in the body, which is what is most informative about your biological age and your average life expectancy. There are several methods that are useful to know, which lengthen your telomeres: exercise, omega-3 fatty acid supplements, vitamin D3 in higher doses and not smoking are all known to lengthen your telomeres. Astragalus, a Chinese herb and extracts (expensive!) derived from this plant have also been shown to increase the length of telomeres. Other factors that help to preserve the length of your telomeres are reducing stress (yoga, meditation, enjoyable music), weight loss through a ketogenic diet, reduction of depression (rebalancing brain hormones), reducing pessimism, and being happy. Did you know that lobsters are blessed with ubiquitous telomerase expression? As a result they turn over 100 years. Humans are not so lucky, but we have access to simple steps that are protecting our telomeres! Dr. Andrews’ company has searched for telomere elongating substances. Through testing of 39 families of chemicals that are stimulating telomerase to elongate telomeres, he found a few that work. However, the main first step should be to concentrate on restoring the diet of our distant ancestors that gave us our genetic make-up. He stated that the Western diet is the worst contributing factor for telomere shortening. The macro and micronutrient difference between our ancestral diet and the modern diets have caused diseases like high blood pressure, heart attacks, stokes, obesity, diabetes, insulin resistance, dementia and cancer. Our modern diets (particularly the high carb/low fat diets) have increased oxidative stress in our bodies from increased reactive oxygen. This reduces our antioxidant reserves. It leads to malfunctioning of the endothelial lining. Other contributory factors are the overfeeding with omega-6 fatty acids from processed foods and cooking oils(such as corn oil and soybean oil and others.). These food infractions lead to a relative lack of the key vitamins A, D, E and K2 that are important to maintain cell function.

7. Telomeres, Aging and Disease

This title was the talk by Dr. Mark Rosenberg, who has been involved with drug research since 1991. This lecture reinforced what Dr. Andrews has said. However, he added a few aspects that are important to mention: “aging promotes aging”; in an aging person there are more circulating free radicals that undermine your health. So it is important, particularly for an older person to take anti-oxidant supplements to stop free radicals from aging you even faster. Dr. Rosenberg has done a lot of research with cancer cells. He noted that the circulation in a cancer or in metastases from cancer is very poor, which is the reason why chemotherapy often does not reach the cancer cells. He also found in the literature and in his own clinical experience that patients with low LDL cholesterol have increased cancer susceptibility. He mentioned that this was a new paradigm. I have recently discussed this in detail in a previous blog. Briefly, LDL cholesterol is the transport form of cholesterol going from the liver to vital organs like the heart or brain. When LDL is oxidized by free radicals from eating too much sugar and starchy foods that are metabolized into sugar, cells are starved of nutrients and oxygen. This sets the stage for cancer cells to develop, which have a metabolic advantage of being able to produce energy by glycolysis rather than by the aerobic metabolic pathway. Smoking and alcohol consumption shorten telomeres and this makes the person more prone to developing cancer.  On the other hand telomerase treatments have been shown to NOT cause cancer, which was a false belief in the past. At this point it is lifestyle changes that are needed to reduce the using up (aging) of telomeres. Resveratrol, vitamin D3, and astragalus all seem to contribute to lengthening of telomeres. The next few years will likely bring more news about this.

Conclusion

I have only been able to give a few highlights of the 21st Anti-aging Congress in Las Vegas. Another highlight was an appearance of Travis Stork, MD from the ER-doctor show on television. He gave a very down-to-earth presentation making 4 points: 1) healthy living starts in the kitchen, 2) “I need you to start working out”, 3) Mind and body are connected (stress can ruin your health) and 4) Get enough sleep (40% do not get enough sleep), because all of your hormone glands are recovering overnight. He concluded by saying: “Make health your hobby!” Another happening later in the conference was the appearance of California’s 38th Governor, Arnold Schwarzenegger. He received the highest honor of the A4M, the 2013 INFINITI AWARD for his leadership role of funding and supporting stem cell research in California.

Each A4M conference seems to have something new to offer every year. There were many other things that I learnt, but in my mind the topics I summarized above stood out from the rest.

More information on:

1. the use of testosterone and other hormones in male menopause:  http://nethealthbook.com/hormones/hypogonadism/secondary-hypogonadism/male-menopause/

2. high blood pressure: http://nethealthbook.com/cardiovascular-disease/high-blood-pressure-hypertension/

3. telomere lengthening by vitamins, minerals and supplements: http://nethealthbook.com/health-nutrition-and-fitness/nutrition/vitamins-minerals-supplements/   In this review I am mentioning a large Chinese study that proved telomere  lengthening with vitamin C and E, but no other vitamins. Other vitamins are still needed as antioxidants to prevent cancer and hardening of arteries.

Last edited Nov. 7, 2014

Dec
21
2013

Buying Into High Carb, Low Fat Myth Makes You Sick

If you are like most people, you probably still think that “healthy grains” like wheat are good for you and are “essential for a well balanced diet”. Ever since Kellogg’s introduced cereal for breakfast and the bagel was invented as a mid morning snack, which has captured the tastes of millions, the Agro Industry and the food industry have lobbied to have “healthy grains” in the food pyramid or on your plate. The very thought of “the daily bread” is deeply ingrained in our culture.

Other agencies like the Heart Foundation, the Academy of Nutrition and Dietetics (formerly “American Dietetic Association“) and the American Medical Association have reiterated this statement over and over until both the public and physicians accepted this as the truth. However, the scientific data does not support this point of view!  It has been a myth!

We are gradually learning that there has been a big misinformation campaign going on as far back as 1984 (and before) when a consensus panel came up with revised normal values for cholesterol and we as the medical profession were told (myself included) to treat high cholesterol levels much earlier and more aggressively than in the past with statins.

Big Pharma is still pushing for this. Now that I am retired for more than three years I can freely write about what is really going on. The truth has already leaked out, but it is not yet common knowledge.

I like to review the switch from the old school of thought that a high carb/low fat diet would be healthy to the new school of thought that a low carb/high healthy fat diet is healthy. Before you panic, sit back, relax and read what I am saying.

Buying into High Carb, Low Fat Myth Makes You Sick

Buying Into High Carb, Low Fat Myth Makes You Sick

A brief history of the high carb/low fat diet recommendation

It was the Framingham Study, which is an ongoing study since 1948 where a large group of people was followed for decades to sort out what causes heart attacks and strokes and how one could develop a program of prevention. This objective at the beginning of the study was very noble and promising. However, as time went on the results from the Framingham Study that were published intermittently appeared to be more and more confusing.

First there was the lipid theory that was based on the observation that high lipids (called triglycerides) and high cholesterol in the blood would cause heart attacks and strokes. It was assumed that it must have been the fats in the diet that would have caused this. Based on this thinking the lipid theory of arteriosclerosis was formulated, a theory trying to explain how heart attacks were caused.

If this theory were true, a lowering of the blood lipids and cholesterol should have lowered the rates of heart attacks and strokes. Many large trials were done and the statins were developed to lower cholesterol. In a recent blog I have explained that this has not lowered the mortality rates from heart attacks and strokes, but instead of admitting that the researchers made a mistake, many are still doggedly holding on to the dogma of the lipid theory. The truth is that the lipid theory has not been proven to be true; the recommendation of a high carb/low fat diet has also not worked out to save lives by preventing heart attacks and strokes. In fact the opposite is true: older people with high cholesterol live longer and have less Alzheimer’s disease than those with lower cholesterol levels in the blood as Ref. 1 has explained in detail. Dr. Perlmutter mentioned a study from the Netherlands (Ref. 1, page78) involving 724 individuals who on average were 89-year old that were followed for 10 years. Those with high cholesterol lived longer than those with low cholesterol, exactly the opposite of what the lipid theory predicted! Specifically, for each 39% increase in cholesterol there was a 15% decrease in risk of mortality. Think about it: the brain and the heart have LDL receptors on their cell surfaces for a reason. The reason is that both vital organs burn fat and need cholesterol to build up the membranes of the brain and heart cells.

Despite this compelling evidence Big Pharma is in denial and you will still find the lipid theory of arteriosclerosis heavily mentioned on the Internet as the only “valid” explanation for how heart attacks and strokes would be caused.

Inflammation as the alternative explanation of arteriosclerosis

Since the mid 1990’s the first reports surfaced to explain that about 50% of patients with normal cholesterol levels still develop heart attacks. In these patients the C-reactive protein, an inflammatory marker, was very high indicating that an inflammatory process likely caused their illness.

Subsequently further research was able to show that the LDL cholesterol, when oxidized by sugar was responsible for clogged arteries in these patients. It also became apparent that diabetics have a much higher risk to develop heart attacks than patients with normal blood sugars. This led to the conclusion by several different research teams that the lipid theory was wrong and needed to be abandoned.

Instead a new theory has developed that explains that heart attacks and strokes develop in patients where free radicals have damaged LDL cholesterol. This oxidizes LDL cholesterol and leads to hardening of the arteries (arteriosclerosis). Sugar from increased carbohydrate intake has a lot to do with this: it leads to glycation of protein causing glycation end products (abbreviated as AGE’s).

This is an appropriate name as it really is the cause of premature aging, of developing wrinkles, of getting premature hardening of arteries and having a 50-fold risk of free radical formation. This in turn will lead to more tissue aging. LDL used to be thought of as the “bad cholesterol” (I myself have used that term in the past). LDL is now known to be the friendly and important transport form of cholesterol, which is sent from the liver to the brain and heart cells that need it for their metabolism. If LDL is oxidized, however, it becomes useless and the heart and brain cannot absorb cholesterol for membrane synthesis via the LDL receptors. The end result is that vital organs like the heart and the brain do not get enough oxygen and nutrients, which leads to heart attacks and strokes. The free radicals that are released from oxidized LDL cholesterol and that circulate in the blood cause an inflammatory response in the lining of the arteries all over the body, which you know as hardening of the arteries (arteriosclerosis).

This may sound complicated, but all you need to remember is that sugar and starch consumption lead to accelerated hardening of arteries in your body, which causes heart attacks and strokes.

Reassessment of what a heart healthy, brain friendly diet is

The above-mentioned research findings require a complete re-thinking of what a healthy diet would be. The villain turned out to NOT be saturated fat (meat, eggs, butter and avocado), but rather TRANS fat (margarine, hydrogenated polyunsaturated fatty acids) and I agree with the FDA that this should be abolished.  Trans fat is full of free radicals oxidizing LDL cholesterol, which we just learnt is causing hardening of arteries. It is sugar and starches that turned out to be the main villain. Omega-6 fatty acids, found in safflower oil, sun flower oil, grape seed oil and canola oil are bad for you also as they lead to inflammation through the arachidonic acid system in the body. Conversely flaxseed oil, omega-3 fatty acids (EPA and DHA) derived from fish oil are very protective (anti-inflammatory) oils, as is olive oil and coconut oil. These latter two are anti-inflammatory monounsaturated fatty acids. Keep in mind that you want to change the ratio of omega-3 to omega-6 fatty acids more in the direction of omega-3 fatty acids, so that the ratio will be between 1:1 and 1:3. Most Americans are exposed to ratios of 1:8 to 1:16 (too many omega-6 fatty acids in fast food and processed foods), which leads to inflammation of the arteries as well.

The new “heart and brain healthy diet” consists of no refined carbohydrates (sugar and starch), but about 45% complex carbohydrates (organic vegetables like broccoli, spinach, cauliflower, Brussels sprouts, peppers, onions, garlic, peppers, Swiss chard, zucchini, asparagus etc.), 20 % protein and 35% saturated and other fats like omega-3 (1:3 mix with omega-6) fatty acids and monounsaturated fats (like olive oil or coconut oil).

According to Ref.1 you can even eat butter, lard and other animal fats provided they come from clean (not antibiotic or bovine growth hormone treated) animals. Dr. Perlmutter (Ref.1) points out that even extreme diets like the Inuit diet with 80% saturated fat and 20% protein leads to longevity with healthy arteries. The patients who died in the many trials including the Framingham Study did so, because of free radicals from sugar, starch and wheat. Wheat contains the addictive gliadin molecule (part of gluten), which makes people eat more sweets and starchy foods. The liver turns the extra calories into visceral fat deposits that in turn cause the release of cytokines like tumor necrosis factor alpha (TNF alpha) and COX-2 enzymes.

This causes inflammation, heart attacks, strokes and cancer.

Contrary to what Big Pharma wants you to know cholesterol is an anti-inflammatory, LDL is a cholesterol transporter (provided it is not oxidized) and HDL is protective of hardening of the arteries as long as the “ratio of total cholesterol to HDL cholesterol” is less than 3.4 for males and 3.3 for females. This is the cholesterol risk ratio used by cardiologists to determine the risk of coronary artery disease. The average risk of this ratio for Americans is 5.0 for males and 4.4 for females. The ideal ratio to strive for is the “1/2 average risk” ratio of 3.4 for males and 3.3 for women (Ref.2).

Paradigm shift in causation of heart attacks and strokes, but also of cancer, and neurological diseases

As pointed out in Ref. 1 there has been a paradigm shift in our thinking about what causes inflammation and what causes all of the major diseases including premature aging. Many physicians are not up to date in this new thinking although it has been in the medical literature since about 1995. In my colleagues’ defense I like to say that they are busy people and they do not always have the time to do their continuing education. However, it is imperative that the public learns about this paradigm shift as it affects literally everyone. In my YouTube video on the home page of www.nethealthbook.com I have talked about this new thinking in the summer of 2012. Now we are learning that there is an anti-inflammatory, cholesterol containing, fat rich diet without refined carbs, but containing ample complex carbs, which is a modified zone diet or a modified Mediterranean diet that will prevent all these diseases. At the same time it is a weight loss diet as cholesterol and fat in your diet stops the liver from producing lipids and triglycerides and helps you to lose weight. Critics will say that it sounds too good to be true, but I agree with Dr. Perlmutter and Dr. Davis, both of whom have provided ample evidence that it is true. Try some of their recipes. Just read Ref. 1 and 2, where recipes are listed in the back part of their books. Or try the recipes I listed for one day in this blog. I am publishing a book entitled “A Survivor’s Guide To Successful Aging” through Amazon.com, which will come out later in early 2014 where you can find recipes for 1 week in the last chapter.

Conclusion

There has been a paradigm shift in the thinking of how hardening of the arteries is caused. Now it is known that an inflammatory process causes it. It is an overindulgence in sugar, starch and wheat products that causes the liver to produce lipids, cholesterol and leads to the “wheat belly” and the “grain brain”. All of this causes cytokines to bring about an inflammatory reaction that affects the lining of arteries causing heart attacks, strokes, but also Parkinson’s disease, MS, autism, asthma, arthritis, epilepsy, Lou Gehrig disease and Alzheimer’s disease (Ref.1). The inflammation does not stop there. If you keep up the high carb/low fat diet, it will lead to various cancers (Ref. 1 and 3). The solution is a diet high in healthy fats (I would call it a low carb/medium high healthy fat diet) as outlined above consisting of 30 to 35% healthy fat, 20% of protein and 45 to 50% of complex carbs, but none of the refined carbs. I have followed such a diet since 2001. I am enjoying that I can now eat  a reasonable amount of healthy fats, which I was not aware of being allowed before I read Ref. 1 and 3, but I continue with the antioxidant vitamins and anti-inflammatory supplements to prevent LDL oxidization. I hope that many of you can benefit from prevention so you can enjoy a healthy life without being a victim of illness or disability.

More information on:

1. arteriosclerosis: http://nethealthbook.com/cardiovascular-disease/heart-disease/atherosclerosis-the-missing-link-between-strokes-and-heart-attacks/

2. paradigm shift regarding hardening of the arteries: My book “A Survivor’s Guide To Successful Aging: With recipes for 1 week provided by Christina Schilling” explains the content of this blog in much more detail.

References

1. David Perlmutter, MD: “Grain Brain. The Surprising Truth About Wheat, Carbs, And Sugar-Your Brain’s Silent Killers.” Little, Brown and Company, New York, 2013.

2. Life Extension: Disease Prevention and Treatment, Fifth edition. 130 Evidence-Based Protocols to Combat the Diseases of Aging. © 2013

3. William Davis, MD: “Wheat Belly Cookbook. 150 Recipes to Help You Lose the Wheat, Lose the Weight, and Find Your Path Back to Health”. HarperCollins Publishers LTD., Toronto, Canada, 2012.

Last edited Nov. 7, 2014

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Nov
30
2013

Statins Can Hurt The Consumer

Lovastatin (Mevacor, from Merck) was the first statin drug approved by the FDA in 1987 as a cholesterol-lowering drug in the US. It made history in helping high-risk heart attack patients reduce their cholesterol levels and has helped safe many lives. But with the detection around 2002 that heart disease is an inflammatory disease, and that measuring the C-reactive protein with a blood test was a better than measuring cholesterol levels in predicting who would be at risk for developing a heart attack, the landscape has changed. Lifestyle changes have also been shown to be very effective in reducing cholesterol, C-reactive protein and triglyceride levels. In fact, lifestyle changes will reduce the risk for heart attacks and strokes. The newest flurry of activity with calls for putting more people on statins (see this recent news article) makes me suspicious that there could be a misrepresentation of the facts.

In this blog I am analyzing the literature to get to the bottom of the facts on reducing risk for heart attacks and strokes. I also come to my own conclusion.

Facts about cholesterol

Cholesterol is a waxy substance that is part of the cell walls and plays a vital role in our metabolism. Liver cell membranes, for instance contain about 30% cholesterol. However, most of the cholesterol in our body comes from metabolism, 20 to 25% from the liver, the rest in the gut, adrenal glands and the reproductive organs, and also from the brain (the myelin sheaths contain a lot of cholesterol). 50% of the body’s cholesterol is recycled through bile salts and reabsorption of cholesterol in the gut (called the enterohepatic pathway).

Cholesterol is vital for cell function, for insulation of nerve fibers (myelin sheaths) and for synthesis of our steroid hormones (sex hormones and vitamin D3, which  is now considered to be a hormone). The medical establishment took most of the information regarding heart attack and stroke prevention from the ongoing Framingham study. This clearly pointed to the importance of lowering the LDL cholesterol fraction (the “bad” cholesterol) and maintaining or increasing the HDL fraction (the “good” cholesterol). When it was realized that concentrating only on lowering cholesterol missed 50% of all heart attacks that researchers refocused and found the missing link, namely inflammation. Inflammation is at the cause of heart attacks and strokes, high cholesterol and lipids were only secondary phenomena. Ref. 2 points out that a comprehensive approach to treating a patient with high cholesterol should involve a combination of treatments aimed at the underlying risk factors for heart disease or stroke in a particular patient. This involves sophisticated blood tests where a metabolic derangement can be pinpointed. It should include measuring cholesterol fractions, lipids, the C-reactive protein, hormone levels and more.

Statins Can Hurt The Consumer

Statins Can Hurt The Consumer

How the traditional thinking about cholesterol has changed

The Framingham study has provided the basis for the drug industry to produce statins until about 2002 when our thinking about cholesterol being the culprit for causing heart attacks has forever changed. Subsequently further research showed that other factors like inflammation of the blood vessels, the metabolic syndrome associated with obesity and lack of exercise were also to blame for causing heart attacks and strokes. Recently more details have come to light, which point to multiple causes like the consumption of too much sugar, too much trans fats, too much salt and eating too much over processed convenience food.  We end up gaining weight, develop the metabolic syndrome and inflammation of arteries (including the coronary arteries of the heart and the brain vessels). It is the lack of nitric oxide in the lining of the arteries, which combined with inflammatory substances from visceral fat are responsible for hardening of the arteries as the ultimate consequence of faulty nutrition and lack of exercise. We also know that oxidized LDL, particularly the very low-density lipoproteins (VLDL), will release free radicals and damage the arterial walls. CoQ-10 is a supplement, which is known to counteract this. One important test that had developed out of the Framingham study is the “ratio of total cholesterol to HDL cholesterol”, which is used by cardiologists to determine the risk of coronary artery disease. The average risk of this ratio for Americans is 5.0 for males and 4.4 for females. The ideal ratio to strive for is  the “1/2 average risk” ratio of 3.4 for males and 3.3 for women (Ref.2). A fit, slim person who eats a low carb, normal fat diet (modified Mediterranean diet) will often have a ratio of only 3.0, well below the 1/2 average risk. The moment you introduce grains in your diet (cereals, bread, pasta) your liver will convert carbs into LDL cholesterol, while HDL cholesterol will drop resulting in a high risk ratio of above 5.0 (often 7 or 8 or more). The LDL will get oxidized and is deposited into your arteries setting you up for coming down with a heart attack or stroke down the road.

How do statins work?

The statins are a group of drugs that inhibit an enzyme, called the hydroxymethylglutaryl–Coenzyme A (HMG-CoA), which leads to a lowering of cholesterol, specifically a fraction known as the LDL cholesterol. The success story of lovastatin (Mevacor) led to a flurry of new HMG-CoA reductase inhibitors (cholesterol lowering drugs) such as fluvastatin (Lescol), pravastatin (Pravachol), simvastatin (Zocor), atorvastatin (Lipitor), and rosuvastatin (Crestor) in the late 1980’s and the 1990’s. Collectively it is now a 26 billion industry in annual sales.

Later investigations showed that there were other mechanisms by which statins helped, namely they were found to decrease the inflammatory reaction, which can be measured by lowering of the C-reactive protein. However, there are significant side effects in about 1 to 3% of people who take this medication, particularly an inflammation of liver cells (evident from elevation of liver enzymes) and a myopathy, which is a painful muscle condition (Ref. 1). This latter fact, which can occur in as many as 33% of the population at large (particularly the exercise minded) has limited the use of statins in competitive athletes where myopathies can occur in as many as 75% of athletes treated with statins (Ref.2). The reason for that is that the muscles of athletes cannot keep up with the demands put on them when they are kept in check by the HMG-CoA reductase inhibitors. On the other hand statins have prevented heart attacks and deaths from heart attacks and strokes in about 25% to 35% of patients treated with them as many clinical trials have shown (Ref.1), but simple supplements that have no side effects can do the same or do even better (see below).

The lack of cholesterol synthesis by the body’s cells when statins are given, leads to an expression of more LDL receptors on the cell surfaces. LDL binds to these receptors and enters the cells, which removes the circulating high risk LDL fraction of cholesterol from the blood thus causing a drop in LDL cholesterol. All of the side effects of statins (pull down to side effects in this link) can be explained as a result of the slow-down of organ functions (brain, muscles, gut, adrenal glands, etc.) as cholesterol synthesis is reduced.

New information from the Framingham Heart Study

So far everything I said made sense. But when I came across Ref. 4 I noticed that there was a bombshell of new information from another follow-up study of the Framingham Heart Study (Ref. 5) that did not fit in with the latest marketing drive of the statin manufacturers. In this study from 2005 Boston researchers had studied the outcomes of 789 men and 1105 women over a period of 16 to 18 years with respect to cognitive function. Participants were divided into total cholesterol groups that showed levels that were desirable (less than 200), borderline (200 to 239) or high (above 240). The astounding results were that higher cognitive functioning as documented in multiple cognitive tests in these three groups showed the best performance in the group with the highest cholesterol and the worst cognitive test outcomes in the lowest cholesterol group, quite opposite of what was expected.

Another important piece of research (April 2013) comes from Spain where doctors followed a group of 7447 patients with a high cardiovascular risk who were put on a Mediterranean diet with olive oil, a Mediterranean diet with nuts or a regular diet. The end point was death from heart attack or stroke. After 4.8 years the study had to be interrupted as the Mediterranean groups showed a significant survival advantage over the group on a regular diet.

Ref. 4 cited literature evidence that statins cause a 48% increased risk in postmenopausal women who take statins to develop diabetes. It also cites compelling evidence that diabetes patients are twice as likely to develop Alzheimer’s disease within 15 years and are 1.75 times more likely to develop any kind of dementia in the same time period.

Dr. Seneff from the Computer Science and Artificial Intelligence Laboratory at MIT explains in great detail that statins effectively reduce cholesterol synthesis in the liver, which in turn starves the brain of one of its main nutrients explaining why patient develop Alzheimer’s disease and dementia as a result of statin treatment.

So, the lessons to be learnt from these clinical trials are that you want to offer your brain enough cholesterol and healthy fat to have a normal metabolism. Fortunately, what’s good for your heart is also good for your brain. Conversely avoid statins, if you can and try alternatives first. Ref. 4 explains that for years the experts had the wrong theory that low fat/high carb was what would be good for your heart and brain, but the opposite is true: what is good for your heart and brain is a high healthy fats/low refined carb diet.

Make sure that with your blood tests that fasting insulin is low (no insulin resistance), that the ratio of total cholesterol to HDL cholesterol is less than 3.4 (low risk for heart attacks or strokes) and that the hemoglobin A1C level is low (4.8 to 5.6%, ideally less than 4.5%), which means you are not diabetic.

How alternative treatment can save you from heart attacks

Lifestyle treatment through dietary intervention, moderate exercise, and weight loss has been somewhat neglected by mainstream medicine, but is now recognized in regular textbooks of medicine as first-line treatment (Ref. 3). Most patients can lower LDL cholesterol by 10 to 15% through a change in diet. High-risk patients with established heart disease (narrowing of coronary arteries) require a drop of 30 to 60% of LDL cholesterol; this high-risk patient group may need an addition of a statin. In patients with metabolic syndrome or diabetes high triglycerides are often present and will respond to decreased intake of simple sugars, alcohol, and calories (Ref.3). Total calorie intake should be adjusted according to what the weight is when weighed every day with the goal of reducing the weight when overweight or obese, but maintaining the weight when it is in the normal body mass index range (BMI of 20 to 25). The total fat intake should be around 25%-35% of the total calorie intake. Specifically, saturated fat needs to be less than 7% of total calories, polyunsaturated fat up to 10% of total calories and monounsaturated fat up to 20% of total calories. Healthy fats according to Ref. 4 are extra-virgin olive oil, organic butter, almond milk, avocados, olives, nuts, nut butters and cheese ( except for blue cheeses). Other healthy fats are sesame oil, coconut oil, and the oils found in seeds like flaxseed, sunflower seeds, pumpkin seeds and chia seeds. Note that trans-fats (such as in margarine and baked goods) are a “no-no” as it causes free radicals in your body, which would accelerate the hardening of your arteries. Complex carbohydrates from vegetables and fruit are the main source of total calories providing 50%-60% of the total calories. Fiber intake needs to be 20-30 grams per day. Protein intake should be about 15% of total calories. Fat should provide 25% to 35% of the total calories per day. Cholesterol intake should be less than 200 mg per day. You may want to consider the use of plant sterols (2 grams per day) to enhance LDL cholesterol lowering. Physical activity from moderate exercise should expend at least 200 kcal per day (better 300 kcal).

Which supplements prevent heart attacks and strokes?

There are several nutrients that have been shown to be powerful preventers of heart attacks and strokes. I will review them briefly here (based on Ref. 2):

1. Coenzyme Q10 (CoQ10): The cells lining the arteries are only working well when their mitochondria are working properly producing chemical energy in form of ATP. CoQ10 is an important component of the mitochondrial metabolism; it is also the only fat soluble antioxidant that gets absorbed into the LDL particles where it protects these from oxidation. Statins suppress CoQ10 synthesis, so patients on statins need to take CoQ10 supplements daily to counteract this. However, anybody who is healthy now should take CoQ10 as a daily supplement for prevention. I take 400 mg per day.

2. Vitamin E (tocopherols): this fat soluble vitamin is an antioxidant and has been praised in the past as being heart supportive, was subsequently bad-mouthed by some conservative physicians, but lately has been resurrected. It turns out that there are 8 different types of tocopherols, with the alpha tocopherol being the most known, but gamma tocopherol is the one you want to make sure you are also getting with your balanced vitamin E supplement every day as this is the one that is a powerful anti-inflammatory. Simply ask staff at your health food store for a vitamin E supplement with gamma tocopherol in it. Take 400 IU per day (of the mix).

3. Curcumin: This is a powerful heart and brain protector combining three different mechanisms in one; it is reducing oxidative stress, is an anti-inflammatory and counters the process that threatens to destroy the lining of the arteries. One study on healthy volunteers showed a reduction of 33% in lipid oxidation, a 12% reduction of total cholesterol and an increase of 29% of the protective HDL cholesterol when 500 mg of curcumin was taken only for 7 days (Ref.2). This is the daily dose I would recommend for prevention of heart attacks and strokes.

4. Polyphenols: Flavonoids are the largest group among the polyphenols contained in such common foods as vegetables, fruits, tea, coffee, chocolate and wine.  Over 130 studies have been done on humans showing improvement of the lining of the arteries (endothelial functioning) and lowering of blood pressure. Polyphenol consumption has been associated with a lower risk of mortality from heart attacks. Eat a Mediterranean type diet or a DASH diet and you will automatically get enough polyphenols with your food. However, resveratrol, the powerful red wine polyphenol warrants a separate daily supplementation as it prevents LDL oxidation in humans (Ref.2). Take about 250 mg of it daily.

5. Niacin/nicotinic acid: This supplement comes as “flush-free niacin” and also as extended release niacin; it can raise the beneficial HDL cholesterol by 30 to 35% when higher doses of 2.25 grams per day are used. In a metaanalysis of 7 studies it has been shown to significantly reduce heart attacks and transient ischemic attacks (precursor syndrome before developing a stroke). Niacin can change the small particle LDL into a large particle size LDL, which is less dangerous. Niacin has also been shown to reduce oxidation of LDL, which stops the atherosclerotic process. For a healthy person 500 mg per day of flush-free niacin is adequate.

6. Fish oil (omega-3-fatty acids): Because heart attacks are due to an inflammatory process and high LDL cholesterol is thought to be only a secondary phenomenon, it is very important to have this additional tool of an important anti-inflammatory supplement. In the past it was still safe to eat fish fairly frequently per week. But with mercury, radioactive iodine from Japan’s leaking reactor and carcinogenic PBC’s all congregating in the ocean waters, it is no longer safe to consume fish in large quantities. The remedy to this situation is molecularly distilled (or pharmaceutically pure) EPA/DHA supplements. EPA stands for eicosapentaenoic acid or omega-3 fatty acid. DHA is the acronym for docosahexaenoic acid. Fish oil supplements at a dosage of 3.35 grams per day of EPA plus DHA were shown to reduce triglycerides by up to 40%, equally to Lipitor or even more effective, but without the statin side effects. The amount of the dangerous small dense LDL is also being reduced with fish oil. Fish oil supplements have reduced the mortality from heart attacks and strokes and led to a higher survival from non-fatal heart attacks. At the same time these preventative fish oil doses will also treat and prevent arthritis.

7. Other useful supplements: Soluble fiber from psyllium, pectin, beta-glucans and others have been shown in clinical trials to reduce LDL cholesterol by binding bile salts in the gut (interrupting the enterohepatic pathway). Plant sterols (usually sold as sterol esters) are recognized by the FDA as reducing the risk of coronary heart disease, if taken in high enough amounts (2.4 grams of sterol esters per day). There are other useful supplements like artichoke extract, pomegranate, soy protein, Indian gooseberry (amla), garlic and pantethine (vitamin B5) that have been proven to be of benefit in terms of prevention of heart attacks and strokes. It would be too lengthy to get into more details here.

Conclusion

Recently there was a review in a medical journal that demonstrated that clinical guidelines (in this case for clinical guidelines for lowering cholesterol) erred 40% of the times when measured against scientific tests as this link explains. When it comes to saving lives by preventing heart attacks and strokes, what is needed is a multifactorial approach that treats the multifactorial causes of cardiovascular disease. Just pushing for treating more people with statins as Big Pharma is attempting to do is not addressing the fact that cholesterol is needed for our metabolism and the synthesis of our hormones. It is much superior to use a combination of different approaches that overlap and thus potentiate each other in their effects excluding statins first. Exercise creates more nitric oxide production by the lining of the arteries, which opens up arteries and prevents spasms. A proper diet with as many of the proven vitamins and other support factors will control inflammation and oxidation of LDL cholesterol particles as explained. This will prevent heart attacks and strokes as has been shown in many clinical trials. Only patients who come from families with genetically high cholesterol or high triglycerides and those patients who had heart attacks and strokes should be exposed to statins as they are at a higher risk of developing a heart attack or stroke. They need all of the help they can get in addition to the lifestyle factors mentioned. Most other patients and the public at large will do quite well without statins (no side effects of diabetes, Alzheimer’s and muscle pains). And, yes, a diet high in healthy fats, but low in refined carbs is what your brain and heart need (the opposite of what you have thought, see Ref. 4).

More information about side-effects of statins (acute pancreatitis): http://www.askdrray.com/pancreatitis-can-occur-with-statin-use/

Lower cholesterol with Mediterranean diet: http://nethealthbook.com/news/mediterranean-diet-benefits-us-workers/

 

References

1. Bonow: Braunwald’s Heart Disease – A Textbook of Cardiovascular Medicine, 9th ed. © 2011 Saunders.

2. Life Extension: Disease Prevention and Treatment, Fifth edition. 130 Evidence-Based Protocols to Combat the Diseases of Aging. © 2013

3. Melmed: Williams Textbook of Endocrinology, 12th ed. © 2011 Saunders.

4. David Perlmutter, MD: “Grain Brain. The Surprising Truth About Wheat, Carbs, And Sugar-Your Brain’s Silent Killers.” Little, Brown and Company, New York, 2013.

5. http://www.psychosomaticmedicine.org/content/67/1/24.full.pdf

Last edited Nov. 7, 2014