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
17
2013

Calcium, Vitamin D3 and Vitamin K2 Are Needed For Bone Health

Introduction

I am reviewing in this blog why calcium, vitamin D3 and vitamin K2 are needed for bone health. Recently there has been a lot of coverage in the press regarding postmenopausal treatment of women to prevent osteoporosis. It is all based on this original publication February 26, 2013.

Essentially, there are a number of studies where researchers did a meta-analysis of several trials. They studied osteoporotic bone fracture frequency in female subjects taking 400 IU vitamin D and 1000 mg calcium daily. The researchers measured the frequency of osteoporotic fractures as the indicator  for osteoporosis in these postmenopausal women. The conclusion was that there was no value in taking these supplements to prevent osteoporosis. Many other media publications carried this story.

No kidney stones in study with calcium and vitamin D3

Just two days earlier (Feb. 24, 2013) another study was released with a much larger patient base of 36,282 postmenopausal women of the Women’s Health initiative in the US who were followed up for 7 years. Initially there confusion how compliant the patients were taking their supplements. The required supplementation consisted of 1000 mg of calcium carbonate and 400 IU of vitamin D3. 7 years into the trial the researchers compared the supplement compliant group with the control group taking placebos.

Calcium and vitamin D3 supplementation significantly reduces risk of hip fractures

The study group had 35% to 38% less fractures of the hip than the placebo group. This supplementation did not cause kidney stones in the study group. This was in contrast to what previous smaller studies showed. Some physicians insisted citing the older studies that vitamin D3 and calcium supplementation would cause kidney stones. But the above study refutes the causation of kidney stones by supplementing with vitamin D3 and calcium. In other words, all of these kidney stone concern you have so often read in the media are not true.

Outline of this review

In order to make sense of supplementation as osteoporosis prevention I will first review what a normal bone metabolism requires.  I will then comment on what is missing in some of the studies and why it still makes sense to supplement to prevent osteoporosis. In addition, at the end of this blog I will also recommend a sensible supplementation regimen.  All this is based on a balanced review of the medical literature.

Calcium, Vitamin D3 and Vitamin K2 Needed For Bone Health

Calcium, Vitamin D3 and Vitamin K2 Needed For Bone Health

Bone metabolism

But vitamin D3, vitamin K2 and strontium together have also been shown to build up bone density within one year.

So, how does vitamin K2 deposit calcium into the bone? Vitamin K2 stimulates a hormone, called calcitonin, which is produced by specialized C cells (parafollicular cells) inside the thyroid gland and released into the bloodstream. Calcitonin arrives in the bone where it binds firmly with receptors of osteoclasts (bone remodeling cells), which stops breakdown of bone. Calcitonin is helped by another hormone, called osteocalcin, which is produced by the bone producing cells with the name osteoblasts.

Vitamin K2 controls osteocalcin, which is a calcium-regulating hormone

The physician can measure osteocalcin levels in the blood and use this as a research tool to see whether a medication is effective in building up bone mass density (BMD). Vitamin K2 control osteocalcin as a calcium-regulating hormone. If vitamin K2 is present, carboxylation of osteocalcin will lead to mineralization of the bone (new bone formation); if vitamin K2 is absent, osteoporosis sets in.

The skeleton of an average adult contains 1–1.3 kg of calcium and 99% of this is mostly in the form of hydroxyapatite.

The key vitamins for bone metabolism are vitamin D and vitamin K2

Calcium absorption from the small intestine requires vitamin D3 (Ref.1). To transport calcium from the blood into the bone we require both vitamin D3 and vitamin K2 (=menaquinone). This blog explains that several studies have shown that vitamin K2 (or MK-7) plays a double role of preventing calcification of the arteries and bringing the calcium into the bones of osteoporotic women.

Apart from Vitamin K2 that is necessary for osteoporosis prevention other factors have shown to be of importance. For instance, testosterone is an anabolic hormone (meaning a hormone that builds up) and it has clearly been shown that it is bone building: It does so by stimulating osteoblasts, which are bone producing cells that reside inside the bone.

Vitamin D3, vitamin K2, Calcitonin and osteocalcin

But vitamin D3, vitamin K2 and strontium together have also been shown to build up bone density within one year.

So, how does vitamin K2 deposit calcium into the bone? It does so by stimulating a hormone, called calcitonin, which is produced by specialized C cells (parafollicular cells) inside the thyroid gland and released into the blood stream. Calcitonin arrives in the bone where it binds firmly with receptors of osteoclasts (bone remodeling cells), which stops breakdown of bone. Calcitonin is helped by another hormone, called osteocalcin, which is produced by the bone producing cells with the name osteoblasts.

Vitamin K2 controls osteocalcin, which is a calcium-regulating hormone

Osteocalcin levels in the blood can be measured and used as a research tool to see whether a medication is effective in building up bone mass density (BMD). Vitamin K2 controls osteocalcin as a calcium-regulating hormone. If vitamin K2 is present, carboxylation of osteocalcin will lead to mineralization of the bone (new bone formation); if vitamin K2 is absent, osteoporosis sets in.

Vitamin K2 also prevents heart attacks and strokes

Vitamin K2 has a second function: it removes calcium from the arterial walls and tissues. How does it do this?

Matrix GLA protein is found in tissues of the heart, lungs, kidneys and blood vessels. When vitamin K2 stimulates carboxylation of this protein, it will function like a broom and clean out calcium deposits (calcification) from blood vessels and organ tissues. As vitamin K2 is needed for this carboxylation process, it appears that nature had in mind to remove calcium from soft tissue organs and blood vessels and form hydroxyapatite in the bone for bone strength.

Vitamin K2 is the key to deposit calcium into the bone

It seems that vitamin K2 is the key vitamin necessary to do this job. Another player is magnesium, which is part of of the normal function of more than 300 cellular enzyme systems. In terms of hormones the three hormones parathyroid hormone (PTH), vitamin D3 and calcitonin need to interact normally, all requiring magnesium as cofactor. In addition, zinc, copper, boron, and manganese are also essential as trace minerals. They act as cofactors with regard to specific enzymes of the bone metabolism (Ref. 1).

Bioidentical hormone replacement essential after menopause and andropause

In the aging person hormonal deficiencies are also factors for causing osteoporosis to develop. As this link shows, Dr. John Lee found bioidentical progesterone topical cream very helpful in women with respect to increasing bone mass density by 15% over 3 years.

When bloods tests show testosterone depletion men need to replace what is missing with bioidentical testosterone. So, bioidentical hormone replacement in both men and women is part of a bone health management program to prevent osteoporosis.

Some trials that demonstrate how you can build up bone

  • In this paper parathyroid hormone  was used in combination with 1000 mg of calcium and 400 IU of vitamin D3 in a group of postmenopausal women with osteoporosis. Within 3 month of treatment there was an increase of bone mass density in the lower back (lumbar spine) of 4.7%, which translates into a yearly increase of bone mass density of 18.8%. In the past when physicians tested other agents for bone regeneration, this type of result never occurred. There is a  variation of this hormone,  a parathyroid hormone look-alike with the name Teriparatide (PTH 1-34). The patient administers this once daily as an injection of 20 mcg up to 2 years. Physicians found this useful in treating fractures of the vertebrae and other fractures in osteoporotic postmenopausal women (Ref.2).

Effect of Vitamin K2, estrogen and calcium citrate supplementation

Calcitonin and calcium strontium

  • Calcitonin is very effective in reducing bone pain when the patient has compression fractures from osteoporosis; the physician can prescribe it as an intranasal spray of 200 units daily (Ref. 2). However, on March 5, 2013 the FDA announced that salmon calcitonin would not be safe for humans as there is a slight risk that cancer can develop as a “side-effect”.
  • According to Ref. 2 physicians sometimes use strontium ranelate in Europe for the treatment of postmenopausal osteoporosis. Researcher showed that strontium ranelate builds up bone and decreases the amount of bone resorption. Side effects include nausea and diarrhea.

The team players of bone metabolism to build strong bone

We are now in a position to analyze why the researchers of the first paper (citation above) concluded that calcium and vitamin D3 supplementation were not enough to make a statistical difference in the treatment of postmenopausal women in comparison to placebos. As explained bone metabolism is a complex process involving several team players, where the key player is vitamin K2, which the researchers of that study ignored completely. The examples I mentioned above in point form show that exercise and calcium are also important. Vitamin K2 by itself worked quite well as it is so powerful. Hormones like PTH and calcitonin are effective, but more difficult to take for the average consumer and the FDA now has banned calcitonin.

Importance of vitamin D3 as a supplement

Vitamin D3 is important for absorption of calcium from the intestine, but also for depositing calcium into the bone in addition to vitamin K2. The WHI study mentioned above is highly significant because of a 1/3 reduction of hip fractures after 7 years of vitamin D3 and 1000 mg of calcium per day supplementation. If you add vitamin K2, exercise and bioidentical hormone replacement in postmenopausal women who need it, the prevention of hip fractures, wrist fractures and vertebral compression fractures likely will be as high as 50% in those who are taking their supplements regularly (compliance issues like forgetting the supplements or deliberately not taking them were mentioned in several of the studies).

Vitamin K2 helps to reduce heart attacks, strokes and osteoporosis

With the right supplementation, which includes vitamin K2 as mentioned above, you achieve that you lower your heart attack and stroke risk as the vitamin K2 removes the calcium from the blood vessels and deposits it into the bones, while at the same time strengthening your bones. Attention to proper nutrition, exercise and your hormone balance (using only bio-identical hormones to replace what’s missing) will also reinforce osteoporosis prevention. The bonus of using bioidentical hormone replacement therapy is that you prevent heart attacks and strokes in addition to preventing osteoporosis. I think that this is a good deal!

An easy-to-follow osteoporosis prevention program

The best combination is 1000 mg (or 1200 mg as per National Osteoporosis Foundation recommendation) of calcium per day together with 400 to 800 IU of vitamin D3 (for cancer prevention you may want to take 4000 IU to 5000 IU of vitamin D3 per day instead monitored by a 25-hydroxyvitamin D blood level test through your physician) and 100 to 200 micrograms of vitamin K2 (also called MK-7). In the age group above 50 several hormones can be missing.

Hormone depletion in menopause and andropause

That’s why the doctor recommends bioidentical testosterone in men and bioidentical progesterone/estrogen combinations in women with hormone depletion. This works best, if you also watch your weight and cut down your alcohol consumption to a minimum. Cutting alcohol out completely would be even better. In addition, exercise regularly as this builds up bone and muscle strength.  It also helps, if you stick to a balanced diet (Mediterranean or Zone type diet). These diets are low-glycemic, low fat, wheat free and without sugar).

If you want to age gracefully, you need not only a healthy heart and a healthy brain. You also need healthy bones as this prevents disabilities.

References

  1. McPherson: Henry’s Clinical Diagnosis and Management by Laboratory Methods, 22nd ed. Copyright © 2011 Saunders, An Imprint of Elsevier
  2. Rakel: Integrative Medicine, 3rd ed. Copyright © 2012 Saunders, An Imprint of Elsevier

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I received the following feedback (Originally on Nov. 10, 2013)

 Dr. Ray, I read your March 17 Blog entry which suggested 100 ug of Vitamin K2 with 5000 IU of D3.   I have atherosclerosis and have radically changed my diet (plant only), but also now take an average of about 3000 IU of Vitamin D3. Dr. Kate Rhéaume-Bleue (book on K2) recommended taking about 200 ug per day of K2, but increasing K2 to about 1,000 ug if taking around 5,000 IU of D3 to ensure proper activation of MGP. What is your opinion with regard to a D3/K2 ration?  Thank you

 Answer from Dr. Ray (Originally on Nov. 12, 2013, modified April 29, 2021)

I appreciate your question about what doses of vitamin K2 to take. There are varied recommendations, but I like to go by human trials and what they have actually shown. In this review in 2010 from the Life Extension Magazine a study is cited that showed that only 45 micrograms of vitamin K2 was enough to get the calcium out of the arterial walls and into the bones.

200 micrograms of Vitamin K2 daily

Dr. Mercola reviewed the literature and found that most investigators were now using 180 to 200 micrograms. In the past I took 100 micrograms of vitamin K2 per day. However, a few years ago I increased it to 200 micrograms per day. With regard to vitamin D3 absorption my anti-aging doctor found that I have an absorption problem regarding vitamin D3. This is why I need 10,000 IU of vitamin D3 daily. This brings my vitamin D blood level up into the high normal range (between 50 and 80 ng/mL). Toxic vitamin D blood levels start only above 150 ng/mL.

Avoid sugar and too much starch consumption

Remember that other risks for cardiovascular disease are sugar and starch consumption. The liver turns this into triglycerides and too much LDL cholesterol, which plugs up your arteries. Avoid wheat because of the gliadin content. This causes an addiction to wheat and sugary foods. Here is a summary how leaky gut syndrome and autoimmune illnesses may develop from this. If you want to consume beef, reduce your consumption to once or twice per week. It id best to stick to only eat grass fed, antibiotic free beef). But I rather prefer to eat organic chicken, turkey and lean pork. I understand that you have a plant only based diet, but I would recommend to you to reconsider that. Ask your doctor to check your ferritin from time to time. This way you do not miss an iron deficiency that may develop. For other readers: Don’t forget your vegetables (organic, please).

More information about osteoporosis: http://nethealthbook.com/arthritis/osteoporosis/

Last updated Nov. 6, 2014

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