Preventing Macular Degeneration: A New Theory

Pioneering Eye Surgeon Sees Hope for Treating Macular Degeneration with Natural Hormones

LIFE EXTENSION MAGAZINE

December 2008

By Debora Yost

Plant caroteinoids such as lutein and zeaxanthin were long ago shown to help prevent macular degeneration. But is there more that can be done to protect against this epidemic of blindness? George W. Rozakis, MD is a Cornell-trained biomedical engineer specializing in laser eye surgery and lens implants. A pioneer in the field of LASIK surgery,1 Dr. Rozakis is now vigorously involved in anti-aging medical research. Dr. Rozakis is focusing on a potential breakthrough in treating macular degeneration, a condition that gradually destroys central vision. Also called age-related macular degeneration, it is the leading cause of blindness in people aged 65 and older. Dr. Rozakis believes that restoring the correct balance of natural hormones that decline with age can retard and possibly even reverse the progression of macular degeneration. To investigate this hypothesis, he is setting up a long-term study and is currently seeking subjects to participate in the trial. Hormones and Your Vision The hormonal link with macular degeneration began to evolve when Dr. Rozakis met another medical pioneer, Sergey A. Dzugan, MD, PhD, during a conference in Chicago four years ago. Dr. Dzugan is a cardiovascular surgeon and internationally known expert in anti-aging and hormonal medicine. “Dr. Dzugan has done numerous studies2-4 and written numerous articles on the association between low hormone levels and multiple disease states, including the problem of atherosclerosis and cholesterol elevation,” says Dr. Rozakis. “As an ophthalmologist I was impressed by the evidence that restoring and optimizing levels of key hormones improve brain function, largely because the retina is part of the brain. For example, there is very impressive literature that testosterone slows down the progression of Alzheimer’s disease.5 Pregnenolone is extremely important for the brain and nervous system, as are progesterone and estrogens. Women whose progesterone levels drop develop negative personality changes.6 In animal models, pregnenolone and DHEA have been shown to profoundly stimulate the healing of neurologic injury.7-9 Women who enter into menopause at a young age develop macular degeneration, presumably because of the absence of estrogens.10,11 Blocking estrogens with the anti-cancer drug tamoxifen is harmful to the retina.12 This leads us to wonder if optimal hormonal health also positively impacts ocular health.” “When an article appeared in the American Journal of Ophthalmology indicating that DHEA, or dehydroepiandrosterone, is exceptionally low in macular degeneration patients,13 I was shocked and excited,” says Dr. Rozakis. This finding provided a major clue that hormonal imbalance was part of the problem of macular degeneration. “DHEA is like the Grand Central Station of hormone chemistry,” says Dr. Rozakis. “When DHEA levels drop, it strongly implies that levels of other hormones such as pregnenolone, estrogens, and testosterone are out of balance or suboptimal.” All of these hormones make the body thrive—they give us virility, fertility, and help us act and react quicker. Since the retina contains hormone receptors, hormones must be part of the biophysiology of vision itself. An eye affected by wet age-related macular degeneration. Details of the back of the retina are shown at upper right. At left are the photoreceptors (red and brown) with the blood vessels that supply the eye behind them in the choroid layer. In wet, or neovascular, macular degeneration, weakened blood vessel formation in the back of the eye can lead to bleeding, which prevents light from reaching the back of the eye. This causes a central spot in the vision as well as distortion, and often leads to blindness. THE ANATOMY OF MACULAR DEGENERATION Macular degeneration, or age-related macular degeneration, is characterized by loss of the sharp, central vision you need to read, drive a car, or watch a movie. Peripheral vision—sight out of the corner of the eye—is not affected. The macula is located near the center of the retina. The retina, a thin layer of cells that resides in the back of the eyeball, contains millions of photoreceptors that capture light and sends signals via the optic nerve to the brain where they are converted into the images that you perceive. Age-related macular degeneration occurs when drusen, tiny yellow particles that consist largely of cholesterol, begin to accumulate behind the eye and damage the photoreceptors, causing degradation of vision. This is known as dry macular degeneration and is the most common form of the disease. Though the disease usually progresses slowly, there is no known cure. Approximately 10% of people with age-related macular degeneration have the wet form of the condition. It is characterized by the growth of abnormal retinal blood vessels that leak, which can cause rapid and irreversible loss of vision. Dry macular degeneration does not always lead to wet macular degeneration, but wet macular degeneration starts off as the dry form. According to the National Eye Institute, risk factors include smoking, poor diet, lack of exercise, high blood pressure, and overweight or obesity. Cardiovascular Link Low DHEA levels in macular degeneration could also explain its association with heart disease, as it is known that macular degeneration is an independent risk factor for stroke and coronary artery disease. In a study conducted by Australian scientists,14 macular degeneration predicted a five-fold higher risk of cardiovascular mortality and a 10-fold higher risk of stroke mortality. After controlling for traditional cardiovascular risk factors, age-related macular degeneration predicted a doubling of cardiovascular mortality. Since hormone deficiency has been linked with both heart disease and eye disorders,13,15 it is a prime suspect that links the heart to the eye. Further examination of the literature reveals a major review article from Italy that explains the importance of hormones to the retina.16 In this article, it is shown that the retina is able to attempt to make its own hormones, just like the brain. “The article also indicates that many of the hormones we use in anti-aging programs have a role in the retina, such as pregnenolone, DHEA, testosterone, estrogens, and progesterone. Few ophthalmologists and optometrists are aware of this relationship. This was the smoking gun that led to our hypothesis,” Dr. Rozakis notes. Macular Degeneration and Cholesterol A good theory needs to connect all the dots. Dr. Rozakis explains that one challenge in shaping his theory was explaining the presence of “drusen” or spots that appear in the retina in patients with macular degeneration. Many consider these spots to be “degradation products.” Recently, Goldis Malek, PhD, and others17-19 found that cholesterol was present in those spots. This led some people to think that cholesterol-lowering agents, such as statins, might help macular degeneration—but they do not. In fact, there is concern that statins actually increase the risk of dry macular degeneration advancing to the neovascular form of the disease, whereby tiny blood vessels in the eye begin to bleed.20 Dr. Rozakis notes, “To Dr. Dzugan and me, the presence of cholesterol in the macula was the key piece of data that integrated everything. The presence of cholesterol in the macula suggests that the retina is trying to make hormones—but that it can’t. So, the body’s accumulation of cholesterol and drusen worsen.” He continues, “The macula can’t get the hormones it needs from the blood because there aren’t much there. As a result, if the macula is having trouble converting cholesterol into hormones, drusen form, and this results in the drusen we see in macular degeneration. Why the macula stops making hormones is unknown, but it is associated with aging. We can speculate that it happens because the enzymes which do the conversion decrease or are down-regulated with aging.” “This same ‘story’ of cholesterol and hormones plays itself out in the body as a whole,” says Dr. Rozakis. “We do know that the adrenal gland, which produces DHEA, loses the ability to manufacture hormones as we age. As Dr. Dzugan published, this hormonal decline stimulates the liver to produce more cholesterol in an attempt to create more hormones.3 This is why restoring hormones to their normal levels causes the liver to produce less cholesterol. That same paradigm may be happening in the macula. This is the basis of our hypothesis. The goal therefore must be to provide the retina the hormones it needs through supplementation.” WHAT YOU NEED TO KNOW: PREVENTING MACULAR DEGENERATION—A NEW THEORY Macular degeneration is the leading cause of age-related vision loss in adults aged 65 and older. The condition is characterized by the accumulation of cholesterol-containing lesions called drusen in the eye’s retina. Since hormones are known to benefit brain health, scientists wondered if they might likewise benefit the retina, which has an embryologic association with the brain. The macular requires hormones to function, and is able to make its own hormones. Recent studies have shown that individuals with macular degeneration tend to have low blood levels of the hormone dehydroepiandro-sterone (DHEA) as well as a higher risk of cardiovascular mortality. These observations led Dr. George Rozakis and Dr. Sergey Dzugan to propose “The Hormonal Theory of Macular Degeneration.” This theory hypothesizes that low blood hormone levels cause the retinal macula to accumulate cholesterol in an attempt to produce its own hormones. The macula’s accumulation of cholesterol may lead to the production of pathological drusen and subsequent macular degeneration. Drs. Rozakis and Dzugan are conducting a clinical study to determine if restoring optimal hormone balance while providing nutrients that support eye health can prevent or reverse the progression of macular degeneration. If you would like to inquire about the study, please call Dr. Rozakis’ office at 440-777-2667. Reviewing the Evidence There is already evidence to support the notion that DHEA protects the eyes against oxidative damage21 and that the hormone pregnenolone improves electrical activity in the retina, as measured by the electroretinogram (ERG).22,23 There is also evidence to support the use of melatonin in the treatment of macular degeneration.24,25 The theory that optimizing hormones may help promote macular health is based on these scientific facts: The macula, which is located in the center of the retina, uses hormones to function.16 The normal macula has the unique ability to make its own hormones.26 The bloodstream of patients with macular degeneration is deficient in hormones.11,13 Drusen—the tiny yellow abnormalities that appear behind the macula in individuals with macular degeneration—contain cholesterol.17-19 Age-related macular degeneration is related to cardiovascular mortality.14 Dr. Rozakis speculates that the solution for treating macular degeneration is to measure and restore age-depleted hormones to optimal levels so that the macula can absorb the hormones it needs from the blood. “Hopefully restoring hormones to their normal levels in the bloodstream will cause the macula to stop absorbing cholesterol and, as a result, drusen formation will hopefully decline,” says Dr. Rozakis. “We certainly need a better understanding of the pathophysiology of this blinding disease.”27 ARE YOU A CANDIDATE FOR THE MACULAR DEGENERATION STUDY? Macular degeneration is diagnosed as either dry (non-neovascular) or wet (neovascular). Neovascular macular degeneration is characterized by the growth of new blood vessels in the macula where they are not supposed to be. The dry form is more common than the wet form, with about 85-90% of macular degeneration patients diagnosed with dry macular degeneration. The wet form of the disease usually leads to more serious vision loss. If you have been diagnosed with dry macular degeneration or have a family history of this disease, you may be a candidate for Dr. Rozakis’ study. The ideal participant is someone with the dry form of macular degeneration, which is characterized by the accumulation of drusen behind the retina, and who still has useful vision (20/80 vision or better, using corrective lenses as needed). Dr. Rozakis says, however, that there are exceptions to this rule. The study involves taking bioidentical hormones—meaning natural hormones such as progesterone, rather than synthetic hormones such as progestin—and a regimen of vitamins that have been found to be beneficial to slowing the progress of age-related macular degeneration. Blood work and a detailed baseline ophthalmology evaluation will be required. The data that will be generated will be compared with other data that already exist on the progression of the disease. The purpose of the study is to measure the progression of the disease. Progress will be measured against currently known standards and the average rate at which the dry form of the disease converts to the wet form. If the program is successful, there should be slower progression, or even reversal, of age-related macular degeneration, and less conversion from the dry to wet form of the disease. Dr. Dzugan will be assisting in this clinical study. Individuals who would like to inquire about the study should call Dr. Rozakis’ office at 440-777-2667. A Higher Level of Natural Treatment Dr. Rozakis sees hormone restoration as a strategy to improve on existing studies showing that certain nutrients can reduce the progression of age-related macular degeneration. The long-term Age-Related Eye Disease Study (AREDS), conducted by the National Eye Institute, found that supplementing the anti-oxidants beta-carotene, vitamin C, vitamin E, and the mineral zinc reduced the risk of developing advanced states of macular degeneration in more than 4,700 high-risk patients aged 55 to 80 who were enrolled in the study.28 The specific amounts of nutrients used by the study researchers were: 500 mg of vitamin C 400 IU of vitamin E 15 mg of beta-carotene 80 mg of zinc 2 mg of copper. The copper, administered as cupric oxide, was included in the formula to prevent copper-deficiency anemia, which is associated with high zinc intake. As a result of the AREDS trial, many ophthalmologists are recommending supplements containing the study’s recommended dosages for patients with or at a high risk for age-related macular degeneration. Dr. Rozakis is currently developing his own study to test his theory concerning the relationship between low levels of DHEA and macular degeneration. “Our study is going to focus on overall hormonal balance and will include the supplements used in the AREDS study as well,” says Dr. Rozakis. “Our goal is to do everything we can to stop macular degeneration. The fact that hormones are much more powerful than vitamins holds hope that the results will be significant.” If you have any questions on the scientific content of this article, please contact a Life Extension Health Advisor at 1-800-226-2370. Article review by Richard P. Kratz, MD, DSci Life Extension Scientific Advisory Board Member Tragically, the leading cause of age-related visual loss is macular degeneration which remains largely untreatable. By the age of 65, nearly one-third of adults or 20-25 million Americans will have experienced some decrease in their ability to read, drive, or see fine details. At present, the cause of age-related macular degeneration is unknown. The disorder is characterized by the development of small yellow spots in the retina called drusen. Theories to explain the occurrence of drusen include accumulation of cellular waste products, age-related reduction of blood flow, inflammation, nutrient deficiency, cigarette smoking, and high fat intake. New strategies for the prevention and management of macular degeneration are sorely needed. The past decade has seen an explosion of interest in managing wellness by restoring hormones. Unfortunately, progress in this arena has been complicated by the use of non-bioidentical, pharmaceutical hormones such as Premarin® (horse urine estrogen). The scientific literature contains many studies examining the use of single hormones, which further confuses the issues at hand. Studies that focus on the balance of all hormones are greatly needed. For example, a study to determine the value of estrogen therapy alone in managing a particular disorder is insufficient, as an estrogen deficiency must be looked at in the context of progesterone levels and other adjacent hormones in the biological hormonal cascades. Today, innovative clinicians are increasingly using bioidentical hormones in their practice. These are true hormones that are identical to those naturally produced by the body, which often become depleted due to the aging process. Examples of these bioidentical hormones include pregnenolone, dehydroepiandro-sterone (DHEA), estriol, estradiol, estrone, progesterone, testosterone, dihydrotestosterone, and cortisol. George W. Rozakis, MD, has been a student of hormonal medicine for a number of years, thanks to his association with Sergey A. Dzugan, MD, PhD, one of the leading experts in hormonal medicine. Dr. Rozakis has proposed a new theory for one of the leading causes of blindness, which he titles “The Hormonal Theory of Macular Degeneration.” The prime mover for this idea is the embryologic association between the retina and the brain. Since hormones are known to benefit the brain, Dr. Rozakis theorizes whether hormones also benefit the macula. When recent scientific literature showed that blood DHEA levels are low in patients with macular degeneration, that the macula can make its own hormones, and that cholesterol is present in the pathological lesions known as drusen, the stage was set for Dr. Rozakis’ theory. LEADING THE FIELD OF VISION-SAVING TECHNOLOGY When it comes to eye health and vision-saving technology, Dr Rozakis is at the forefront as a visionary, an inventor, and a pioneer. In 1989, he was one of the first surgeons in the world to perform LASIK refractive eye surgery, and he went on to advance the technique by developing and refining his own patented laser system incorporating LASIK surgery.1 Now used worldwide, the technique is often called a modern medical miracle that eliminates the need for eyeglasses. Seeing that LASIK is not the solution for all refractive lens problems, the 53-year-old graduate of Cornell Medical College and the Duke Eye Center has now pioneered next-generation technology that will likely make LASIK obsolete: a very thin lens that can be permanently implanted into the eye and which, unlike LASIK, can be reversed. Dr. Rozakis postulates that cholesterol-containing drusen are the retina’s failed last-ditch attempt to make needed hormones, including DHEA, from cholesterol. Such a failed attempt leads to the findings we see in the retina, namely the small yellow spots called drusen. If Dr. Rozakis is correct, restoring normal hormone levels should help to prevent macular degeneration and might even improve early-stage macular degeneration. This is a novel idea, which he intends to test in clinical trials. His theory is in keeping with the modern trend of measuring hormone levels and then administering hormone replacement to re-establish hormonal balance and restore health. Careful clinical trials will be required to evaluate Dr. Rozakis’ hormonal theory of macular degeneration.

References

1. Available at: http://patft.uspto.gov/netacgi/nph-Parser? u=%2Fnetahtml%2Fsrchnum.htm&Sect1=PTO1&Sect2=HITOFF&p=1&r=1&l=50&f=G&d=PALL&s1=5843070. PN.&OS=PN/5843070&RS=PN/5843070. Accessed September 16, 2008. 2. Dzugan SA, Smith RA. Broad spectrum restoration in natural steroid hormones as possible treatment for hypercholesterolemia. Bull Urg Rec Med. 2002;3:278-84. 3. Dzugan SA, Arnold SR. Hypercholesterolemia treatment: a new hypothesis or just an accident? Med Hypotheses. 2002 Dec;59(6):751-6. 4. Dzugan SA, Smith RA. Kuznetsov AS. A new statin free method of hypercholesterolemia. The Health of Donbass. 2004;4:19-25. 5. Driscoll I, Resnick SM. Testosterone and cognition in normal aging and Alzheimer’s disease: an update. Curr Alzheimer Res. 2007 Feb;4(1):33-45. 6. Andreen L, Sundstrom-Poromaa I, Bixo M, Nyberg S, Backstrom T. Allopregnanolone concentration and mood--a bimodal association in postmenopausal women treated with oral progesterone. Psychopharmacology (Berl). 2006 Aug;187(2):209-21. 7. Li H, Klein G, Sun P, Buchan AM. Dehydroepiandrosterone (DHEA) reduces neuronal injury in a rat model of global cerebral ischemia. Brain Res. 2001 Jan 12;888(2):263-6. 8. Bucolo C, Drago F. Effects of neurosteroids on ischemia-reperfusion injury in the rat retina: role of sigma1 recognition sites. Eur J Pharmacol. 2004 Sep 13;498(1-3):111-4. 9. Guth L, Zhang Z, Roberts E. Key role for pregnenolone in combination therapy that promotes recovery after spinal cord injury. Proc Natl Acad Sci USA. 1994 Dec 6;91(25):12308-12. 10. Boekhoorn SS, Vingerling JR, Uitterlinden AG, et al. Estrogen receptor alpha gene polymorphisms associated with incident aging macula disorder. Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1012-7. 11. Smith W, Mitchell P, Wang JJ. Gender, oestrogen, hormone replacement and age-related macular degeneration: results from the Blue Mountains Eye Study. Aust N Z J Ophthalmol. 1997 May;25 Suppl 1:S13-5. 12. Vinding T, Nielsen NV. Retinopathy caused by treatment with tamoxifen in low dosage. Acta Ophthalmol (Copenh). 1983 Feb;61(1):45-50. 13. Tamer C, Oksuz H, Sogut S. Serum dehydroepiandrosterone sulphate level in age-related macular degeneration. Am J Ophthalmol. 2007 Feb;143(2):212-6. 14. Tan JS, Wang JJ, Liew G, Rochtchina E, Mitchell P. Age-related macular degeneration and mortality from cardiovascular disease or stroke. Br J Ophthalmol. 2008 Apr;92(4):509-12. 15. Thijs L, Fagard R, Forette F, Nawrot T, Staessen JA. Are low dehydroepiandrosterone sulphate levels predictive for cardiovascular diseases? A review of prospective and retrospective studies. Acta Cardiol. 2003 Oct;58(5):403-10. 16. Guarneri P, Cascio C, Russo D, et al. Neurosteroids in the retina: neurodegenerative and neuroprotective agents in retinal degeneration. Ann NY Acad Sci. 2003 Dec;1007:117-28. 17. Malek G, Li CM, Guidry C, Medeiros NE, Curcio CA. Apolipoprotein B in cholesterol-containing drusen and basal deposits of human eyes with age-related maculopathy. Am J Pathol. 2003 Feb;162(2):413-25. 18. Li CM, Clark ME, Rudolf M, Curcio CA. Distribution and composition of esterified and unesterified cholesterol in extra-macular drusen. Exp Eye Res. 2007 Aug;85(2):192-201. 19. Curcio CA, Presley JB, Millican CL, Medeiros NE. Basal deposits and drusen in eyes with age-related maculopathy: evidence for solid lipid particles. Exp Eye Res. 2005 Jun;80(6):761-5. 20. Available at: http://www.medscape.com/viewarticle/573810?src=rss. Accessed September 16, 2008. 21. Bucolo C, Drago F, Lin LR, Reddy VN. Neuroactive steroids protect retinal pigment epithelium against oxidative stress. Neuroreport. 2005 Aug 1;16(11):1203-7. 22. Jaliffa CO, Howard S, Hoijman E, et al. Effect of neurosteroids on the retinal gabaergic system and electroretinographic activity in the golden hamster. J Neurochem. 2005 Sep;94(6):1666-75. 23. Binns AM, Margrain TH. Evaluating retinal function in age-related maculopathy with the ERG photostress test. Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2806-13. 24. Lundmark PO, Pandi-Perumal SR, Srinivasan V, Cardinali DP. Role of melatonin in the eye and ocular dysfunctions. Vis Neurosci. 2006 Nov;23(6):853-62. 25. Yi C, Pan X, Yan H, Guo M, Pierpaoli W. Effects of melatonin in age-related macular degeneration. Ann NY Acad Sci. 2005 Dec;1057:384-92. 26. Guarneri P, Guarneri R, Cascio C, Pavasant P, Piccoli F, Papadopoulos V. Neurosteroidogenesis in rat retinas. J Neurochem. 1994 Jul;63(1):86-96. 27. Zarbin MA. Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol. 2004 Apr;122(4):598-614. 28. Schutt F, Pauleikhoff D, Holz FG. Vitamins and trace elements in age-related macular degeneration. Current recommendations, based on the results of the AREDS study. Ophthalmologe. 2002 Apr;99(4):301-3

https://www.lifeextension.com/magazine/2008/12/preventing-macular-degeneration/page-01

Vitamin K2 Deficiency Is a Significant Cause of Cardiovascular Disease

You may be watching your vitamin D and calcium to "grow strong bones," but inadvertently be placing yourself at higher risk for cardiovascular disease. If you take these medications or eliminate this from your diet, you could be raising your risk.

July 13, 2016 

Story at-a-glance

• Warfarin and statins may reduce your absorption of vitamin K2, leading to an increased risk of heart disease, stroke, osteoporosis and cancer
• Although necessary for your overall health, vitamin D without vitamin K2 may increase your risk of atherosclerosis, heart disease and stroke
• Vitamin K2 is found in fermented foods, fermented cheeses and grass-fed meats and dairy products

By Dr. Mercola

Your body is a complex organism, dependent upon the interactions and interrelationships of organs, enzymes, vitamins and hormones. Anytime you take a nutritional supplement, especially at high doses, you affect the balance of others.

For instance, if you take a zinc supplement, you must be wary of a copper imbalance in your body. These two nutrients balance each other, meaning you may suffer from either zinc or copper toxicity if they get out of balance.

The same is true for vitamins K and D. When the ratio between these two is not balanced, it can increase your risk for cardiovascular disease (CVD), stroke and heart attacks.

But vitamin supplements are not the only thing that can cause an imbalance. In a recent review, researchers found a link between medications used to lower cholesterol levels and treat type 2 diabetes and an inhibition of absorption of vitamin K from food.1

The 2 Forms of Vitamin K

In this video, Dr. Kate Rhéaume-Bleue discusses the differences between vitamins K1 and K2 and how they interact with vitamin D, calcium and other nutrients.

Vitamin K was discovered in 1929 as part of an experiment and was associated with blood coagulation, or how your blood clots.2 There are two main forms of the vitamin. Phylloquinone (K1) is found in leafy green plants and menaquinone (K2) is found in animal meat and fermented foods. Your body can also synthesize K2 in your gut.

Vitamin K2 can be divided into subtypes. The two we understand to be important today are MK-4 (short-chain) and MK-7 (long-chain bacterial derived).

Both vitamins K1 and K2 have important functions in your body. K1 is an integral factor in blood clotting and K2 activates proteins that regulate where calcium ends up in your body.3

The importance of vitamin K2 relates to the interaction it has with calcium. How and where calcium is deposited and used by your body has an impact on your dental health, bone health, cardiovascular system and renal (kidney) health. Each of these bodily systems depend upon the correct balance of calcium.4

Your body has limited storage capacity for vitamin K2, but can recycle the vitamin so it can be used multiple times.5 The functions of the vitamin are unique and necessary throughout all your life stages.

Many Drugs Reduce Vitamin K2 Absorption

The review paper associated medications used to treat cardiovascular disease (CVD) and type 2 diabetes with an inhibition of vitamin K2 processes. These negative effects may increase your risk for CVD, diabetes, chronic kidney disease, bone loss and even mental disorders, as a result of poor K2 absorption.6

The research found a shared mechanism between the blood thinner warfarin, statin medications and vegetable oils in the inhibition of vitamin K dependent processes.7The blood thinner warfarin works to reduce coagulation through an antagonistic effect on vitamin K.

This was the design of the drug. Even eating foods with vitamin K can reduce the effectiveness of warfarin. Research has also found that:

• Anti-tuberculosis medications or anticonvulsant medications, taken when you are pregnant, may place your newborn at increased risk of vitamin K deficiency8
• Use of broad-spectrum antibiotics may alter your gut microbiome and thus reduce the effectiveness of your gut to synthesize vitamin K2. Drug classes associated with this alteration include cephalosporins and salicylates9
• Statin medications, developed to reduce cholesterol levels, also have a negative impact on your vitamin K2 absorption and inhibit CoQ10,10 both necessary for a healthy cardiovascular system.

Dr. Hogne Vik, chief medical officer with NattoPharma, a leader in vitamin K2 research and development, says:11

"We are not only finally seeing recognition that vitamin K2 is woefully insufficient in the diet, but there is a growing body of evidence that pharmaceuticals further exacerbate the problem of our limited vitamin K2 status, delivering potentially dangerous consequences for human health."

Interaction Between K2 and Your Cardiovascular System

A significant risk factor in the development of CVD is calcium buildup in your arterial system.12,13 Plaque formation on the walls of your arteries may lead to small pieces breaking off, causing clot formation. This is one of the more common reasons for a heart attack or stroke.14

Calcification of these plaque formations occurs as atherosclerotic disease progresses, which may predict your risk for future cardiovascular events.

A meta-analysis of 30 studies, including over 218,000 participants, found calcification in the arteries was associated with a 300 to 400 percent increased risk of a cardiovascular event (such as a heart attack) or death.15

Vitamin K2 regulates arterial calcification through protein modulation. In one study, those who had the highest amount of vitamin K2 were 52 percent less likely to experience calcification in their arteries and 57 percent less likely to die from heart disease over a seven to 10 year period.16

Insufficient vitamin K2 in your diet may also lead to suboptimal carboxylation and biologically inactive matrix carboxylated glutamate protein (MGP), both leading to lower protection of your cardiovascular system from calcification of the arterial system.17

Vitamin D and Vitamin K2 Need Balance

Vitamin D influences or plays a significant role in dozens of conditions, including:

Eye health	Preventing macular degeneration	Preventing dry eye
Immune system health	Preventing bowel disease	Reducing effects of rheumatic diseases
Reducing effects of multiple sclerosis	Reducing effects of lupus	Fighting HIV/AIDS
Reducing depression	Reducing potential for childhood asthma	Reducing the risk of certain cancers
Reducing the signs of aging	Prevention of dementia	Prevention of heart disease

Deficiency in vitamin D may also contribute to a number of different health conditions, all of which increase your risk of heart disease. These conditions include high blood pressure, type 2 diabetes, atherosclerosis and increased inflammation in your body.18

However, like most other vitamins and nutrients, no one nutrient operates independently of others. For instance, most pasteurized milk is fortified with vitamin D. Manufacturers recognize they have effectively eradicated the natural vitamin D in the milk, necessary for absorption of calcium, and so they add it.

While vitamin D helps you absorb calcium, vitamin K2 directs your body to deposit the calcium in the appropriate places. In other words, it's the vitamin K2 that tells your body to deposit calcium in your bones and teeth, and not in your organs, arteries, muscles or soft tissue.

An effective analogy is that vitamin D is your gatekeeper, allowing the admission of calcium, and vitamin K2 is the traffic cop, telling the calcium where to go. With vitamin D and calcium you'll have the traffic, but without vitamin K2 you'll have a traffic jam and calcium being deposited exactly where you don't want it — in your arteries.

With the push for vitamin D and calcium to "grow strong bones," you may be at risk for CVD if your diet isn't rich in sources of vitamin K2. As an added risk, you may be taking medication or have an altered gut microbiome, reducing the absorption of vitamin K2.

Role of K2 in Osteoporosis

Osteoporosis causes more than 8.9 million fractures worldwide. This means a fracture due to osteoporosis happens every three seconds.19 Worldwide, 1 in 3 women and 1 in 5 men over the age of 50 will experience a fracture related to osteoporosis.

The strength of your bones is related to several factors. Both the density of the bone and formation of the bone are related to the strength of the bone. When you have density without proper formation, your risk of fracture may actually increase. Your body needs several nutrients to build strong bones.20

Vitamin K2, working together with vitamin D, magnesium, phosphorus and calcium, helps your body develop strong bones and may reduce your risk of osteoporosis. This is because nutrients in your body are interconnected in the way they function.

Vitamin K is essential to the proper development of several bone-related proteins, including osteocalcin, MGP and periostin. Vitamin K is also a cofactor in the production of gamma-glutamyl carboxylase (GGCX). Recent research links low levels of GGCX and/or vitamin K2 to bone mineralization defects.21

This means that without vitamin K2 your body produces bone with defects, reducing the strength of the bone and increasing your risk of bone mineralization fractures.22,23

Vitamin K2 Is Also Important for Your Teeth and Cancer Prevention

Vitamin K2 also plays a significant role in the health of your teeth and in preventing cancer. You teeth, like your bones, are storehouses of calcium, which supports the structure and hardness of the teeth.24 The way calcium is deposited in your teeth will either increase the hardness of your tooth or make it more brittle.

Vitamin K2 once again acts like the traffic cop, telling calcium where and how to be used in your teeth. Working together with vitamin D, it also promotes a reduction in tooth decay or cavities.25 The process of depositing calcium in areas of the body where it is not normally found may act like sand in the gears of a machine. In fact, inappropriate calcium distribution may contribute to the development of:

Gallstones	Colon cancer
Liver cancer	Ovarian cysts
Bone cancer	Breast cancer
Prostate cancer	Lung cancer
Dementia	Leukemia
Varicose veins	Macular degeneration

German doctors evaluating the effect of vitamins K1 and K2 on the development and treatment of prostate cancer found that those who consumed the greatest amount of K2 had a 63 percent reduced incidence of advanced prostate cancer.26,27

Vitamin K2 has demonstrated the ability to induce cell destruction in leukemia cells outside the body.28 The vitamin also demonstrated inhibitory effects on myeloma and lymphoma. Following treatment for liver cancer, those who took K2 supplements experienced a 13 percent relapse of the cancer while those who did not experienced a 55 percent relapse rate.29,30

Enjoy the Benefits of K2

How do you know if you're deficient in vitamin K2? According to Rhéaume-Bleue, there are several questions you can ask yourself, and depending upon the answers, you'll have a good idea if you are deficient. Estimates suggest up to 85 percent of Americans are vitamin K2 deficient.

•Do you suffer from health conditions associated with vitamin K2 deficiency? Some of these conditions are listed above.

•Do you eat meats, dairy or cheeses from grass-fed sources? Grass-fed beef and the dairy products from these animals are higher in vitamin K2 and healthier for you.

•Do you eat fermented foods? The bacteria in the fermentation process produce vitamin K2 in the food. Natto (fermented soybeans), is one of the best sources of vitamin K2. I ate it for a while, but the flavor is a bit of a challenge and probably isn't well accepted by the Western palate.

Other fermented foods like kimchi also contain vitamin K2. My favorite way of getting K2 is to ferment my own vegetables using a special starter culture designed with bacteria that produce K2.

•Do you eat Brie or Gouda cheeses or consistently eat liver pate? Fermentation in the cheese produces vitamin K2. Fermented dairy products will provide about one-third the amount per serving of natto. Ideally, I recommend fermented cheeses from raw milk. It is important to note that raw milk in and of itself does not contain K2. The vitamin is produced during the fermentation process.

If these foods aren't a regular part of your diet, then you are likely deficient in vitamin K2 and you may benefit from using a supplement. At this time, there are no reliable tests to determine your level of vitamin K2. However, while it is a fat-soluble vitamin, there is no known toxicity at any dose.

It is important to take your supplement with foods containing healthy fat to increase absorption. Of the two forms of vitamin K2, MK-4 and MK-7, the latter is the more effective supplement to use.

MK-4 is a synthetic product, having a very short biological half-life of about one hour, making it a poor candidate as a dietary supplement. After reaching your intestines, it remains mostly in your liver, where it is useful in synthesizing blood-clotting factors. MK-7 is a newer agent with more practical applications because it stays in your body longer. Its half-life is three days, meaning you have a better chance of building up a consistent blood level. MK-7 is extracted from the Japanese fermented soy product, natto.

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