Iron Therapy and Oxidative Free Radicals – Part III

January 30, 2018 Philip Miller Comments 0 Comment

We talked about the essentials of iron metabolism, iron uptake and iron control in part 1 and 2. Now let’s try to unravel the mystery of iron therapy. But first we take a side trip into oxygenation, reactive oxygen species (ROS) and free radicals.

In reading through the literature it is obvious this is a very complex subject. Far more complex than is usually admitted. And I have alluded to many controversies where another binary choice is offered. Either you are leery of iron therapy because it is dangerous and unhealthy or you are an advocate of the multiple benefits of iron.

It’s not an easy choice. I am showing you why iron is so important and beneficial. So let’s delve into the reactive aspects of iron. Then we can come to a happy and more beneficial conclusion.

Free Radicals and Reactive Oxygen Species (ROS)

There is a major and ongoing controversy. Oxidative versus antioxidant therapies. The literature and current belief is replete with references to iron promoting free radicals or ROS (reactive oxygen species). In other words, iron would be considered unhealthy because of its pro-oxidative properties. Consider the “Fenton reaction. Adding Ferric Iron + Hydrogen Peroxide to form Ferrous Iron + Free Radical Oxidative Species.

Figure 2

Now I have always maintained the action of antioxidants is overly simplified. There are structures that should be protected from reactive oxygen species. Namely cell wall structures, mitochondria and DNA. On the other hand, white blood cells depend upon highly reactive oxidative zones to kill bacteria or to have anticancer properties.

Oxidative Therapies vs. Anti-Oxidant Therapies

The debate rages on. I have many colleagues who are strenuously pro-oxidative advocates. They treat cancer and other infectious processes with hydrogen peroxide and/or ozone (triple oxygen) therapies.

One of the prevailing theories of aging is oxidation. It is one of the four pillars of aging in my book Life Extension Revolution. That is, oxidation hastens aging. Much like metallic iron oxidizes and rusts. I have always postulated that over-oxidation is unhealthy.

There is newer thinking that is evolving. It is possible that a small amount of free radicals or reactive oxidative species actually engages and causes a protective and homeostatic reaction. There is a process called hormesis. A small amount of poison introduced in a system stimulates a protective response.

So that a small amount of oxidative free radicals actually induces a beneficial reaction. But the system can become overwhelmed with too many reactive species in which case there is a negative and pathologic effect.

Chemotherapy and Radiation Therapy

Chemotherapy and radiation therapy are examples of highly reactive oxidative reactions that kill cancer cells. That is how they work. So here we have the ultimate example of oxidative therapy. But it is not specifically targeted. So that there is collateral damage. Killing normal cells as well as cancer cells.

And there is a prevailing caution in the oncology community that antioxidants should not be used during chemotherapy or radiation therapy. It might cancel effects of these cancer therapies. This has never been proven to be true. It is only an unproven presumption.

Iron as a Pro-oxidative element

Now why this discussion? Because it assumed that free iron is so highly reactive and potentially oncogenic (causes cancer). Or it promotes and feeds cancer. But within the context of the above discussion, I contend that this has never been definitively proven. It is simply the prevailing theory. This is the genesis of iron causing cancer.

There is definitive no proof that free radicals de novo (by themselves) cause cancer. There is no proof that iron by itself causes cancer. Just like my highly controversial assertion that cholesterol does not cause cardiovascular disease and hormones do not cause cancer. Over time these assertions are gathering more merit and acceptance.

Iron Deficiency and Therapy Next

This was originally going to be a 3 part series. Now maybe 4 or 5 parts. So you can easily digest what is important to you. So you can understand all aspects of iron deficiency and therapy. And why this is such a vital topic which needs a new and refreshing view.

Iron Regulation Part II: Transport Signaling

January 21, 2018 Philip Miller Comments 0 Comment

All these years I was trying to understand the relationship between serum free iron, bound transferrin iron, storage as ferritin iron and anemia. What is the control mechanism? What is the cause of iron deficiency? How is this related to chronic anemia? How much lab data do we need to determine true iron status? OK. So let’s review iron cycling through each body compartment.

Bivalent Iron

You want lab data that measures all these forms of iron transport and storage for a complete and accurate assessment.

Iron exists in two states (bivalent). Ferrous Fe² iron is a reduced state which is more easily absorbed. Ferric Fe³ iron is the more reactive oxidized state. It is less easily absorbed. Ferric iron generates free radicals which can damage tissues and DNA. I will show you later why the more reactive form of iron generates so much controversy.

transport and reversible conversions of ferrous and ferric iron — fig 5

Figure 6 shows the traversal of iron into various key compartments. Here is what is important.

Iron Transport

Dietary iron in the ferrous form is transported across the gut (enterocytes) into the blood stream. Intra-vascular ferrous iron is enzymatically converted to the more reactive ferric iron by ferroxidase. It is then bound to Transferrin. This carrier binding protein transports iron throughout the blood to various tissue sites.

Iron then enters the cells of the liver, spleen, muscle and bone marrow. Inside each cell, iron is bound to Ferritin. This storage protein is capable of binding large quantities of ferric iron. By encapsulating ferric iron, it protects cellular components from reactive free radical damage.

Ferritin is key. I stressed this in part I. Remember, ferritin can also represent inflammation.

The most important compartment is entrance into the bone marrow. That is where red blood cells are manufactured. It is the incorporation of iron into erthryocyte (red blood cell) hemoglobin that is critical for oxygen carrying capacity. Remember, anemia results in oxygen deficit at the cellular level.

Myoglobin is essential for muscle oxygenation. Most especially the muscles of your heart. Hemosiderin is denatured ferritin.

Iron transport from ingest iron to cellular storage — fig 6

Here is the take home message. You want lab data that measures all these forms of iron transport and storage for a complete and accurate picture.

Hepcidin — Master Controller of Iron Regulation

Now here is my recent discovery and “aha” moment. Hepcidin (1) is the x-factor that I had been missing. It is a liver derived protein that has pro-homonal signaling activity. It is a key regulator of iron absorption. [From the latin hep = liver and cidin = killing.]

Hepcidin, a peptide hormone which is mainly synthesized in the liver, was discovered in 2000. It reduces extracellular iron in the body by several mechanisms: 1) It lowers dietary iron absorption by reducing iron transport across gut mucosal cells (enterocytes); 2) It reduces iron exit from macrophages, the main site of iron storage; and 3) it reduces iron exit from the liver. In all three instances this is accomplished by reducing the transmembrane iron transporter ferroportin. — Wikipedia

Hepcidin protein regulates iron absorption — fig 7

How Hepcidin Controls Iron Absorption

Any signal that increases hepcidin levels decreases iron absorption. Contrariwise, any signal that decreases hepcidin will increase iron absorption

I know. It’s complex picture. But simply put, hepcidin determines efficiency of iron absorption. Any signal that increases hepcidin levels from the liver decrease iron absorption. Contrariwise, any signal that decreases hepcidin will increase iron absorption. You can see in fig 7 that the genetic abnormality hemochromatosis is characterized by a deficiency of hepcidin activity. This causes an accumulation of abnormally toxic iron levels. Inflammation is a major signal for increased hepcidin activity thereby causing anemia.

Hepcidin is a regulator of iron metabolism. Hepcidin inhibits iron transport by binding to the iron export channel ferroportin which is located on the basolateral surface of gut enterocytes and the plasma membrane of reticuloendothelial cells (macrophages)…

Inhibiting ferroportin prevents iron from being exported and the iron is sequestered in the cells.^[9]^[10] By inhibiting ferroportin, hepcidin prevents enterocytes from allowing iron into the hepatic portal system, thereby reducing dietary iron absorption …

Increased hepcidin activity is partially responsible for reduced iron availability seen in anemia of chronic inflammation, such as renal failure.^[11]— Wikipedia

That’s a quick overview and background of the complexity of iron transport and control. So how do we correct these deficiencies and improve your iron status? There is a rich array of opinions, guidelines and approaches. That is the subject of the next part III. So stay with me.

Hepcidin – the Iron Regulatory Hormone, Clin Biochem Rev. 2005 Aug; 26(3): 47–49.

To be continued in Part III — How and Why to treat iron deficiency anemia

Iron Metabolism Part I: Sources, Transport, Testing

January 11, 2018 Philip Miller Comments 1 comment

The Essentiality of Elemental iron

Iron is essential for healthy red blood cell hemoglobin levels. Red blood cell hemoglobin is essential for oxygen transport. Oxygen and glucose are absolutely essential for brain function. The topic of today’s review.

I think iron metabolism, assimilation and transport is highly misunderstood. And the subject of great controversy. Here is why. Hemoglobin is the essence of red blood cell function. And you can see in figure 1, iron is the essential core of hemoglobin. Healthy red blood cells transport oxygen. In plants, magnesium is absolutely essential for chlorophyll function.

Hemoglobin is essential for healthy red blood cells (erythrocytes) — fig1

Red blood cells pass through the vasculature of your lungs. Oxygen is inhaled and absorbed by the circulating red blood cells. This is how oxygen is transported to the rest of your body. Your heart, brain and all other vital organs.

red blood cells transport and release oxygen — fig 2

There is a widely held belief that iron supplementation is only essential for younger women especially and not as necessary in postmenopausal women. Similarly iron is believed to be less essential for men as we grow older. This is based on monthly menstrual cycles were iron is shed. In reality these differences in age are not that significantly different.

Sources of Iron

Iron is ingested in food sources or supplements. Beef, chicken liver, oysters, sardines, lentils, spinach.

But the plot thickens.

There is an important difference between heme-iron from red meats and seafoods and non-heme sources. Heme-iron is much more readily and efficiently absorbed. Non-heme sources are much less efficiently absorbed. All plant-based sources are non-heme iron. Additionally many plant based sources contain phytates, polyphenols, or soy that further inhibit efficient iron absorption.

This is why plant based diets so frequently lead to significant iron deficiency anemia. A source of heated controversy.

Elemental salts are also considered non-heme based. That would be ferrous sulfate, ferrous gluconate and ferrous fumarate salts. So simply looking a charts labeling the iron content of each nutrient is not enough. Chelated iron sources may lie in between.

heme-iron and non-heme-iron sources — fig 5

Now let’s look at the continuum of iron deficiency to iron deficiency anemia. You can be iron deficient without suffering anemia. But eventually when iron levels are further depleted true iron deficiency anemia occurs.

Lab Testing — Hematology

Iron deficiency anemia is characterized by very small red blood cells – termed microcytosis. The MCV (the mean corpuscular volume) is a laboratory measure of your red blood cell size. An MCV < 88-90 infers iron deficiency.

Figure 3

[The values in the above diagram are Australian values. Divide the hemoglobin values by 10 for American values. ]

Similarly an MCV > 100 (macrocytosis) raises the possibility of B12 or folate deficiency. .

These are not absolutes. They are general principles. There other conditions that raise the MCV. Alcohol is a major contributor to large (dysfunctional) red blood cells.

In Hematology we measure red blood cells and white blood cells. In the past a centrifuged (spun down) sample would contain a percentage of red blood cells with a top layer of serum. The percentage of sampled red blood cells is called the hematocrit (Hct). Today’s modern labs use flow cytometers so the hematocrit is inferred and not directly measured.

Hematologists have traditionally follow hemoglobin and not hematocrit. Which is probably more descriptive. We want to know how much hemoglobin is available. That is the oxygen carrier or transporter. In simple terms the hematocrit = 3 x hemoglobin.

Most labs use these ranges:

Hct (women) 34-46% <34 is anemic optimal > 38
Hct (men) 39-52% < 39 is anemic optimal > 44
Hgb (women) 11-15 <11 is anemic optimal > 13
Hgb (men) 12-17 < 12 is anemic optimal > 14

In practice, I use much tighter ranges. You are relatively anemic well before you reach these critical cutoff values. I have denote optimal values vs. strict lab cutoff values.

The third measurement is the actual RBC count. Your red blood cell mass.

Hematocrit
Hemoglobin
RBC count
MCV

Iron Metabolism and Transport

Iron transport in various compartments — fig 4

The movement and transport of iron is complex and subject to various controls. Figure 4 shows the movement of iron through these various “compartments.”

It is transported in the blood by attaching to transferrin. A large binding protein complex. It enters cellular storage through the control of ferroportin.

It is stored intracelluarly in the cellular cytosol as ferritin. The ferritin complex is a stable protective protein that neutralizes the reactive aspects of free ferrous (Fe³) iron.

Ferritin is the primary measure of stored iron. It is also a acute phase reactant. A biomarker of inflammation. This confounds ferritin as a simple measure of iron storage because it can also represent an inflammatory process.

Lab Testing — Iron BioMarkers

Now you can see from diagram 3 that measuring or following simple serum iron levels is inadequate. It is only a partial measure of iron sufficiency or deficiency. It is variable. To obtain a more accurate assessment and picture you must obtain:

Serum iron
Transferrin Iron saturation
Ferritin levels
TIBC (total iron binding capacity)
Serum transferrin receptor (sTfR) (added for subtle early signs of iron deficiency)

Ferritin is a measure of stored iron. Serum iron measures free floating iron. Because of insurance-based cost containment, ferritin is not routinely included in current laboratory testing. You definitely want ferritin levels.

Now the picture is even richer for the transport of iron. It becomes quite complex. Actually, far more complex than even I had ever imagined. I have often wondered about the relationship between ferritin (stored iron) and serum iron (free floating iron). What is the controlling factor or mechanism?

stay tuned for Part II — signals that control iron absorption

Flu Vaccine 10% Effective

January 9, 2018 Philip Miller Comments 10 comments

Flu vaccine may only be 10% effective this year? That means 90% ineffective. Tell me more.

I am asked frequently by my patients, “do you suggest or advocate the flu vaccine.” My simple answer is no. I do not recommend flu vaccines. I am middle of road on vaccines. Some vaccines are essential. No argument. Tetanus boosters, MMR for measles, mumps and rubella, polio vaccine. In my day we all had smallpox vaccination. That is now history.

I can vividly remember lining up at my high school for the first series of oral polio vaccinations. It was a new era. Based on the original Jonas Salk vaccine and later refined as the Sabin Vaccine. It was the Sabin vaccine that we all eagerly took on sugar cubes. [many years later Larry Sabin, his son, was one medical school graduating class behind me]

Now the problem with the flu vaccination is quite different. Every year the current strain mutates or originates in a different vector or region. It is subject to antigenic drfit. There is minor antigenic drift and major antigenic drift.

Vaccine Effectiveness by Varies by Year

Major manufacturers of the vaccine only have 6-8 months lead times. The current stock is always based on last year’s strain. With the assumption that there are only minor changes. The minor antigenic drift. But it is never identical. In the best of years, the vaccination is 40-60% effective. Or contrariwise, 40-60% ineffective.

This year, CDC experts are admitting it will only be 10% effective. 90% ineffective or not worth the bother.

So I am greatly puzzled why all hospitals and large institutions mandate the flu vaccination. “It’s better than nothing.” 10% effective is not “better than nothing.” It gives rise to a false sense of security. Staff and patients are protected. No they are not. This is where public safety and good epidemiological policy making collides with individual choice.

Here is a news story from 2004. We have not seen significant change since then.

WASHINGTON – The influenza vaccine that many Americans clamored for this year was not very good at protecting people against influenza, colds and similar viruses, a preliminary report published Thursday shows.

The study is the first attempt to show whether the vaccine that many sought after a flu scare this autumn and winter actually worked.

The study of hospital workers in Colorado, a state that was hit early and hard by influenza, showed the vaccine had “no or low effectiveness against influenza-like illness,” the U.S. Centers for Disease Control and Prevention said in its report.

Reporting this year:

What’s more, this year’s flu shot may not be up to the task. It is the same formulation that was used during Australia’s most recent flu season — which typically sets a pattern for what the U.S. will face — and it was only 10 percent effective there.

… But Sabeti says even though the effectiveness of this year’s vaccine is particularly low, it’s still worthwhile to get a flu shot.

“Even 10 percent effective is better than nothing, and a lot of it has to do with herd immunity — the more people are protected from it, the more other people will also be protected,” she said. “In fact, in a year where it’s low effectiveness, it’s even more important that everybody get it so we can get as much resistance and we don’t allow the virus to thrive and grow and keep changing.” — CBS news

Searching for the Holy Grail — the Universal Vaccine

Researchers are avidly seeking the “universal vaccine.” That is the Holy Grail. An admission that the current crop of vaccines has been admittedly inadequate.

Recent efforts have focused on the development of a new generation of influenza vaccines that could provide broad spectrum, “universal” protection against a wider range of influenza variants including strains with pandemic potential. DNA vaccines possess a number of characteristics that make them particularly well suited for a universal influenza vaccine [3–6]. In the event of a pandemic threat, DNA vaccines offer an important advantage of accelerated vaccine development and production since the DNA vaccine sequences can be obtained directly from the clinical isolate and rapidly constructed and propagated using well-established molecular techniques without the need for cell culture or eggs. DNA vaccines induce both antibody and T cell responses, and both arms of immunity contribute to cross-protection against different influenza variants [7, 8]. — PLOS One

Anti-Viral Medications and Treatment

As recently as 1990’s the common wisdom offered was, “there is no treatment for the flu.” That was not true. And it always puzzled me. It was quite well known even then that Symmetrel (Amantidine) used for Parkinson’s Disease was effective against the flu. From empirical observations it was noted that Parkinson’s patients treated with Symmetrel were far less likely to suffer the seasonal influenza. I began treating patients in walk-in clinics appropriately.

Today we have a new series of anti-viral flu treatments. The most effective is oseltamivir (Tamiflu). A second choice is zanamivir (Relenza). These need to be started in the first 48 hours for maximal effectiveness.

The authoratative and erudite source The Medical Letter concludes:

A neuraminidase inhibitor, either oseltamivir (Tamiflu) or zanamivir (Relenza), remains the drug of choice for treatment of patients with influenza who are at high risk for complications of the disease, and for anyone hospitalized with presumed influenza. Oseltamivir is preferred for treatment of pregnant women. Otherwise healthy persons who are not in a high-risk group generally do not require antiviral prophylaxis or treatment for influenza

A most interesting conundrum. If anti-viral prophylaxis is not indicated for healthy individuals then why is the flu vaccine indicated for everyone? And the debate continues. While there is policy decision-making consensus on flu vaccination, the debate as to the appropriateness of anti-virals continues. I argue here that anti-viral treatment is far more effective per case than vaccination.

Dr. Miller’s Novel Approach

Which finally leads me to a more novel and less toxic approach that has been effective across a wide variety of viral and flu syndromes:

High dose Vitamin D — 50,000 units daily for 5 days (yes, that is high dose)
Astragalus 1000 mg daily for 5 days. A most potent Chinese herb known for its potent immune boosting properties
Thymic Protein A — 1-2 packets three times daily for 5 days. Activates anti-viral t-cell and b-cell immune activity.

Philip Lee Miller, MD

Jan 09 2018

Carmel, CA

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Why Your Doctor Is Either Depressed or Retiring

February 19, 2017 Philip Miller Comments 1 comment

Why Your Doctor Is Burned Out or Retiring

There is a growing litany of acronyms and alphabet soup organizations and algorithms that are designed to confuse, obfuscate and subordinate physician discretionary thinking. Funneling physician thinking into more pre-defined and standardized patterns. With the notion that these patterns are always superior, more efficient and accurate. More than traditional physician discretionary thought, observation and formulation of diagnosis and treatment plans.

This dizzying array is one of the many reasons why virtually every physician over the age of 65 is retiring. You are losing an entire generation of extremely well educated and experienced physicians. The ones who cared. Who were trained to observe. Who were taught to exhaust all testing means. To use deductive and inductive logic.

We have entered the era of economic zero sum medicine. Simple agents of health insurance reimbursement schemes. A world in which medicine becomes thoroughly and inexhaustibly politicized. That is what is being played out in Washington today.

Do you care?

ACO = Accountable Care Organization
MA = Medicare Advantage, original Medicare + choice
ACA (aka PPACA, patient protection and affordable care act) – disastrously branded as ObamaCare
MSSP = Medicare Shared Savings Programs (built into the ACA).
MUHIT = Meaningful Use of health information technology
GPRO = Group Practice Reporting Option (CMS provider value modifier, 2010 present
MACRA = Medicare Access and CHIP Reauthorization (an acronym within an acronym)
- MIPS = Merit Incentive Payment Systems (has 4 components)
  - ACI = Advancing care information (replaces MUA’s IT).
  - CPI = Clinical practice improvement activities
  - TCoC = Total cost of care (usually expressed as annual cost per beneficiary)
  - Quality = replaces the PQRS (physician quality reporting system)
- APM = Alternative payment models
SGR = Sustained growth rate physician formula (1997 – 2016)
RAF = Risk adjustment factor (adjustment used for and a payments)
HCC = Hierarchical condition category (codes that derive the RAF)
TIN = Taxpayer identification number
CMS = Center for Medicare Services — formerly HCFA (Healthcare Financing Administration)
CPC+ = Comprehensive primary care plus (a CMS driven Advance Primary Care Medical Home Model)
CPT = Current procedural terminology (procedure or billing codes)
ICD-10 = Diagnosis coding module currently used in the United States (supersedes the ICD-9)
VM or PVBM = Value Modifier or physicians value-based modifier
CAHPS = Consumer assessment of healthcare providers and systems (HCAHPS, CGCAHPS, HHCAHPS, OASCAPS, etc.)
HiTECH = Health Information Technology for Economic and Clinical Health Act (HITECH Act)

Makes your head spin. Doesn’t it? My mission is and has been the development of a new HealthCare paradigm. Health and Well Being for the next twenty years. Enhancing your healthspan. Enhancing cognitive function (smarter brains). You are going to need it in these times.

Compounding pharmacies – a vanishing breed

February 12, 2017 Philip Miller Comments 0 Comment

Compounding Pharmacies – Service like it used to be

Why are my prescription medication prices increasing and not reimbursed?

Compounding pharmacies and the individualization of specific formulations is an integral part of antiaging, age management, functional medicine and similar holistic practices. There was a time in the distant past when most formulations were compounded. That is the source of the mortar and pestle that was so ubiquitous in all pharmacies. I think that symbol has vanished.

Mortar and pestle – universal sign of pharmacy

The advantage of compounding is preparation of very specific formulations, combinations and dosages. There are many nonstandard dosages that are not commercially available. Compounding pharmacies is a very dedicated group of highly professional caliber. Really good people. The old-fashioned pharmacist is rapidly vanishing. Maybe the same with solo private practices.

Stifling regulation and pressure from Big Pharma has contributed to the steady decline of compounding pharmacists throughout the Bay area and probably across the state of California. This is not a healthy trend. Furthermore, you have seen most of the major insurance carriers are progressively denying all your compounded medications. Under the ruse of FDA non-approval. That is not the reason. They want you to buy prescription medications from large pharmacies. At a very high premium.

The one constant is an accelerating increase in the cost of all medications. I have never been an advocate of insurance coverage of medications. I know this a losing proposition. But it contributes to the subsidization of ever-increasing price increases. Medication prices are out of sight. And now that the major carriers are denying more and more coverage. So you are left with high prices without the subsidies. You are then forced into generic formulations. Generic drugs do not have the same degree of quality assurance and consistency as proprietary medications. I do not recommend generic preparations.

Stifling and onerous regulations – USP 800

Here is a very personal summary of the onerous regulations in the state of California that will contribute to a manifest decline in the number of compounding pharmacists. And further price increases because of the costs of preparation. This is a direct quote from my good friend, Dana Gordon of CAPRx. One of the best pharmacists in the business. A Pharm.D. A doctor of pharmacy with an advanced degree.

Well, “D-Day” or “USP 800-Enforcement Day” has arrived. Effective Jan 1, many substances that were commonly compounded under normal environmental/exposure conditions must now be handled/manipulated under specific environmental areas (dedicated, externally vented, negative pressure room with a minimum 13 air changes per minute . Also externally vented source capture units/hoods within the room).

Let me be clear, the drugs/substances have ALWAYS been considered “hazardous” if an individual was exposed to them at certain levels and under certain exposure routes (i.e. respiration, mucous membranes). Although the list is quite extensive (see NIOSH link attached), some of the ones you are familiar with are: Progesterone, Estrogen, Testosterone, Thyroid, Anastrazol, Retinoic Acid, Fluconazole to name a few.

Understand, the language in USP 800 was pretty much already in existence for many years. What occurred is the renumbering of the chapter to an “enforceable” chapter. Prior to this, the chapter was only “voluntary”. Now, in addition to our 3 (three) accreditations for compounding that hold us accountable to this chapter, we now are potentially subject to FDA oversight should we be in violation of USP 800. Very few pharmacies are as decorated as we are. Our choice, our standards, our commitment to our patients, our providers and ourselves.

Although I have previously communicated with you the significance of this new law, its broad and extensive effects it will have on the compounding industry, and the enormous economic/cost impact it will have on those that have decided and/or are able to comply with the newly implemented regulations, both its repercussions and effects will now become quite evident.

In a nutshell and in summary

1)      California version of USP Chapter 800 becomes effective Jan 1, 2017 (All California pharmacies must be compliant on this date)

2)      Official version of USP Chapter 800 becomes effective July 1, 2018 (California Pharmacies still must be compliant Jan 1, 2017)

3)      Hazardous Drug-Definition: See attached definition. Really, nothing has changed and nothing new has been discovered about the handling of all of these drugs. The purpose of USP 800 is to protect the individuals handling and manipulating such substances. How this will be translated to patients will require some delicacy and discretion. Regardless, literature will be provided with each drug categorized on the NIOSH list. This is a requirement. Also, such substances will be dispensed separately in a plastic back titled “Hazardous”. Also a requirement.

4) CAPRx has been painfully, expensively (over $200K and still counting) invested in preparing for this eminent enforcement date for over a year. Also taxing was the BUD (Beyond-Use-Date) limitations that USP (795 and 797) has determined and now the California State Board of Pharmacy will enforce. All of this at the detriment of causing delays in the production and provision of compounded drugs.

Minivelle Vivelle Shortages Explained

December 12, 2016 Philip Miller Comments 4 comments

Minivelle and Vivelle continue to be in short supply in most pharmacies across the country. Initially, I was not able to determine any reason. Nothing revealed by simple Google searches. No FDA drug recalls. Not evident from FDA drug shortage surveillance lists.

Now, one of my astute and persistent patients was able to track down the reason. The FDA has been very critical of testing and quality assurance methods for this product. Adherence to CGMP. Current Good Manufacturing Practices. The reasons seem sound but are not technically safety related.

Here is the full FDA warning letter which is long and tedious. It is illuminating for you.

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Minivelle Vivelle Short Supply

December 8, 2016 Philip Miller Comments 24 comments

Minivelle and Vivelle are severely backordered. We have not been able to determine the source of this short supply. It emanates from the manufacturer. This is not a local pharmacy problem it is not a distribution problem. For obscure reasons it is not being manufactured. We have not seen any recalls.

The 0.1 mg dose is in most demand and in short supply. Many of you have been dispensed a generic form of estradiol patches. Mylan is the leading generic house. Generic patches are not the same as the proprietary drug — Minivelle or Vivelle dot.

Estrogen patches are not about the drug which is bioidentical. It is 17-beta-estradiol. That is bioidentical. Biologically identical to your own internally produced hormones. The FDA prohibits the manufacturer labeling this as bioidentical. That is a legal-political issue. Not a medical issue.

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Vitamin K, Calcification and GLA Proteins

October 10, 2016 Philip Miller Comments 8 comments

Vitamin K2 is a potent anti-calcification nutrient via GLA protein carboxylation. Let’s look at this process of calcification and the potency of these various forms of vitamin K2. Then talk about the MK-4 vs Mk-7. Which is best for you? And why?

Vitamin K2 forms

There are currently three forms of vitamin K available. Vitamin K1 (phylloquinone) has been extensively studied. It is not the most potent form. Vitamin K2 is currently available in two forms. MK-4 also known as menaquinone-4 or menatetranone. MK-7 (menaquinone-7) is currently advocated as the most potent form of vitamin K2. You can see in fig 1 that the MK-4 and MK-7 have long “tails” with multiple (poly unsaturated) double bonds. This increases lipid solubility. These are fat soluble as opposed to water vitamins.

Vitamin K1 and vitamin K2 MK-4 MK7 — fig 1

So what is the connection between Vitamin K2 and tissue calcification? Why do we petrify as we grow older? Why do we grow stiffer? This is a combination of calcification and glycation. Glycation is secondary to excess carbohydrates, rising hemoglobin A1c (>5.6%), and impaired fasting blood sugars (>100 mg).

Calcification is an impaired healing process. Arterial injuries initiate a process of calcium deposition as a repair mechanism. Calcification is the end result of chronic inflammatory processes. This is a key concept.

How can we prevent or reverse this ossification process?

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Your Personal Supplement Prescription for Optimal Health

August 18, 2016 Philip Miller Comments 5 comments

Supplementation Regimen Can Optimize Your Health

Patients often ask how do you maintain your health and youthfulness? What do you personally take? I need to walk the walk and practice what I preach. I need to set an example for you.

You can do this. You may need our help and motivation. There are many variations of this rigorous approach. You do not need to follow this implicitly. But the closer you can approximate this, the better your results.

For 20 years I have advocated the same routine. The basic approach is consistent. Variations on a theme. The Paleo diet. Low Carb. Modified Atkins diet. Basically high protein low carbohydrate. You can read the classic Protein Power by Michael and Mary Eades.

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