Final Most Common Drug Nutrient Depletions (1)

Most Common Drugs that Cause Nutrient

DepletionsPresented at: Dilworth Drug & Wellness Center

Joseph HelmsWingate University School of Pharmacy

Objectives• List drugs that cause, discuss the pathophysiology, and signs and

symptoms of Drug Nutrient Depletions• Discuss Treatment and Treatment Benefits of Drug Nutrient

depletions including counseling points, commonly discussed drug-drug interactions, cost, storage, and kinetics• Describe the Natural Role of Drug Nutrient Depletion Treatments in

the Body• Discuss Relevance of this Information to Dilworth Drug and to Patients• Summarize Conclusions & Important Takeaways

Epidemiology• 4.27 billion prescriptions are estimated to be filled in 2016• 262.5 million courses of antibiotics written in the U.S. (50% may have

not been appropriate)• 119 million prescriptions for Proton Pump Inhibitors (now available

Over-The-Counter) in 2009• 16% of women aged 15-44 are using “the pill;” 7.2% are using long-

acting contraception (IUD or contraceptive implant)• From 2003-2012 the use of statins increased from 18% to 26%; 42% of

the patients used simvastatin; 17% of adults aged 40-59 used a statin whereas 48% of adults age > 75 used a statin• 259 million prescriptions written for painkillers in 2012

All sources of statistics listed in beginning of other References

General Risk Factors for Drug-Nutrient Depletions

• Elderly•A higher dose of the medication; sometimes

physicians will increase the dose of a medication thinking it has benefit, but the additional dose provides no benefit to the patient, and will ultimately deplete the patient of nutrients• Longer duration of use of the medication• Taking multiple medications that have high risk for

causing drug-nutrient deficiencies

Common Reasons Patients Do Not Take Supplements or Take Low Quality

Supplements for Nutrient Depletions• “I already have a probiotic.”• “I believe I will hold off on that today.”~cost of the supplements• “I already have some CoQ10. I haven’t taken it in a while.”• “I don’t have a B12 deficiency, so why do I need to supplement with it?”• “I don’t like that it’s a liquid. Do you have it in a tablet?”• Patients may not think it will work• Patients may fear that because they are already taking a supplement that by taking

another supplement they may experience toxicity, as well as fear they are taking the wrong dose

• Patients may think that “feeling bad” as you age is normal (healthy aging is preferred)• Patients may not feel they are educated on supplements, and are afraid to ask• Patients may not understand the cost-savings benefit that living a healthier lifestyle may have

Common Concerns/Questions from Providers

• “There have been minimal to no studies to show that supplements are effective. So why would the patient waste their money on this?”• “The supplement may interact with the patient’s medications.”• “Do these supplements correlate with improvement of quality of life

for the patient?”• Providers may not know where patients are purchasing supplements

from, and may be afraid to recommend supplements (even if know pharmacy where patient is getting prescriptions)

Our Job as a Team & Opportunities• Recognize the common drug-nutrient depletions• Communication: Remind other team members of drug nutrient depletions

when possible• Discuss the drug-nutrient depletion with the patient• Readily be able to find product on the shelf, and know what’s in stock• Be able to provide patient basic information about drug-nutrient depletion,

while being able to provide some information that will “Wow” the patient• Be able to discuss with patient why products we sell are of the highest quality• If concerned about drug interactions or other concerns about supplement can

set up consultation with Josh

Knowledge & Customer Service• If do not have basic knowledge of supplement, then it is much harder to

communicate to the patient why the supplement may help them• Must be expressed on patient level, and in way that catches patient’s attention• Opportunity: Can refer patients to Josh for a consultation

• “CoQ10 may improve muscle pain caused by statins.” • It is necessary to know when a patient should be on a supplement due to a drug

nutrient depletion, and there are also other opportunities that may be used to improve a patient’s overall health that may need to be taken into consideration• Opportunity: Must remember that most physicians/providers have very little

time to spend with patients, and have to treat the patients’ most acute problems• Can make patients feel that at pharmacy everyone is interested in their overall health and

well-being, because have time to spend with patients discussing all health problems

Drugs That Cause Nutrient Depletions

Drugs that Cause Nutrient DepletionsAntibiotics

Statins

Metformin

PPIs

Birth Control

Match the Drug with the DepletionDepletion

“Good Bacteria”

CoQ10

Vitamin B12Magnesium, Calcium, and others

Probiotics, Magnesium, Zinc, any B Vitamin, Vitamin C

Cohen, Suzy. Drug Muggers: Which Medications Are Robbing Your Body of Essential Nutrients—and Natural Ways to Restore Them [Internet]. Rodale; 2011. Common Drug Muggers [cited 2015 October 12]; [p.91-92]. Available from: Amazon

Drugs that Cause Nutrient Depletions

Antibiotics

Statins

Metformin

PPIs

Birth Control

VitaminsWater-Soluble- Vitamins that are dissolved in

water, not stored in the tissues of the body though they pass through the tissues of the

body, and must be taken every day; not as easy to build up toxic levels as fat soluble vitamins

Fat-Soluble- Vitamins that are stored in fat in the tissues of the body; easier to build up toxic

levels of these-Known As ADEK

Vitamin B Vitamin AVitamin C Vitamin D

Vitamin EVitamin K

MineralsMacrominerals Trace Minerals

Calcium ZincMagnesium CobaltPotassium CopperChloride Fluoride Sodium Iodine

Potassium IronPhosphorus Manganese

Sulfur SeleniumChromium

“The Solar System”

Metformin: Vitamin B12

Birth Control:Probiotics,

Mg, Zn, any B Vitamin,

Vitamin C

Proton Pump

Inhibitors & Antacids:

Mg, Ca

Statins: CoQ10

Antibiotics: “Good

Bacteria”

Drug Nutrient Depleted State

Earth- “Where no drug nutrient depletion exists.”


“A Negative Plus A Negative Still Equals A…”

ACE Inhibitors

Oral Contraceptives

All May Deplete

Good Bacteria


When Planets Collide in the “Black Hole?”

MetforminAntibiotics: (Especially

Chloramphenicol)

Oral Contraceptives

All May Deplete B Vitamins

Metformin StatinsAll May Deplete CoQ 10


When Planets Collide in the Black Hole (continued)

Proton Pump

Inhibitors/Antacids

Antibiotics Birth Control

All May Deplete

Magnesium and

Calcium


Possible Common Combinations of Drugs Patients May Be Prescribed That Cause Depletions

Medications Depletions

Antibiotics, Metformin, & Glyburide All May Deplete B Vitamins (especially B12 for diabetic medications)

Statins, Antidepressants (i.e., amitriptyline), Beta Blocker, (i.e., atenolol, metoprolol) Calcium Channel

Blockers (i.e., nifedipine, verapamil, amlodipine), Clonidine, Methyldopa, & Metformin

All May Deplete CoQ10

Proton Pump Inhibitor (i.e., omeprazole), Antibiotics, ACE Inhibitors (i.e., lisinopril), Diuretics (i.e.,

furosemide), Colchicine, Oral Contraceptives, Salicyclates (i.e., Aspirin), Medications for Thyroid (i.e.,

Synthroid, Armor), and Laxatives (i.e., Mineral Oil)

All May Deplete Magnesium and CalciumColchicine: Only Calcium

Oral Contraceptives: Especially Magnesium (when taken with ACEI or Diuretic any may deplete Zinc)

Salicylates: Only CalciumThyroid Medications: Only Calcium

Mineral Oil: Particularly CalciumAntibiotics & Oral Contraceptives “Good” Bacteria


Antibiotics Most Likely to Cause DiarrheaMost Likely to Cause

DiarrheaDiarrhea Type

Amoxicillin, Augmentin (Amoxicillin/Clavulanate)

AmpicillinCefpodoxime (3rd generation

cephalosporin)

Cefixime (3rd generation cephalosporin)

Clindamycin Clostridium difficile (bacteria) or C. difficile

How Antibiotics Cause Diarrhea • Antibiotics may cause a depletion of the “good bacteria” in

the small and large intestines which allows more room for bad bacteria to grow• There are approximately 40-100 trillion bacterial cells in the

body (though this number varies), and are found particularly in the large intestine• Commonly said bacterial cells would weigh 2-3 lbs. • There are about 10-30 trillion human cells • Up to 1000 different species of bacteria live in the large intestine• However, 30-40 species of bacteria make up 99% of these species

How Antibiotics Cause Diarrhea• Antibiotic-associated diarrhea often begins a week after start

taking the antibiotic, but the diarrhea may appear even up to several weeks later• Risk Factors: Past Medical History of Antibiotic Associated

Diarrhea, Long Duration of Therapy, and Polypharmacy• Large part of immune system tissues are in same area the

Gastrointestinal tract

Antibiotic Associated Diarrhea• Symptoms/Diagnosis:• Watery Stools• Loss of Potassium • Increased Bowel Movements• No pathogen identified (though cultures may not be reliable)• Risk Factors: Use of Antibiotics, Immunocompromised, Elderly, Children, Abdominal

Surgery, Other Comorbidities, Decreased Gastric Acid (PPI), and Length of Hospital Stay• Prevalence: 3.2-29.0%, 14% in those who do not undergo treatment• 10-20 % of these are from Clostridium difficile

• Clostridium Difficile:• Anaerobic, Gram Positive Rod

Common “Good” Bacteria“Good Bacteria”/Probiotics

Lactobacillus acidophilus(NCFM), Lactobacillus plantarum (Lp-115, HEAL-9),Lactobacillus paracasei (Lpc-37, 8700-2), Lactobacillus delbruekeii subspecies

bulgaricus (reclassified as L. helveticus), Lactobacillus rhamnosus (GR-1), Lactobacillus reuteri (RI-14), Lactobacillus salivarius (Ls-33),

Bifidobacterium lactis (Bi-07, Bi-04, HN019), Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantalis

AcidophilusEscherichia coli

Saccharomyces boulardi (yeast, not bacteria based)Streptococcus thermophiles(St-21)

Common “Bad” Bacteria“Bad” Bacteria

Enterococcus faecalis Lactobacilli

Bacteroides Staphylococci (particulary Staph aureus)

Eubacterium Listeria

Peptococcus Bacilli

Peptostreptococcus Legionella

Ruminococcus (genus of Clostridia) Streptococci

Clostridia

Probiotics & Bacterial StrainsProduct Name Bacterial Strains

UltraFlora Restore 30 ct Bifidobacterium lactis Bi-07, Lactobacillus acidophilus NCFM, Bifidobacterium lactis Bi-

04, Lactobacillus paracasei Lpc-37

UltraFlora Immune Booster Lactobacillus paracasei 8700-2 ~500 million, Lactobacillus plantarum HEAL 9 ~500 million

UltraFlora Balance 60 ct Lactobacillus acidophilus NCFM, Bifidobacterium lactis Bi-07

Florajen 4 Kids Bifidobacterium lactis Bi-07 >3.5 billion, Bifidobacterium lactis HN019 >1 billion,

Lactobacillus acidophilus >1 billion, Lactobacillus rhamnosus > 0.5 billion


Probiotic 25 Billion CFU with/3% Prebiotic FOS

Lactobacillus acidophilus 12.5 billion CFUBifidobacterium lactis 12.5 billion CFU

Florajen 3 (30 ct) Lactobacillus acidophilus >7.5 billionBifidobacterium lactis > 6 billion

Bifidobacterium longum >1.5 billion

VSL #3 Probiotic Medical Food (60 capsules)

Streptococcus thermophiles, Bifidobacterium breve, Bifidobacterium longum,

Bifidobacterium infantalis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus

delbruekeii subspecies bulgaricus (reclassified as L. helveticus)


Women’s Probiotic (2 capsules= 1 serving size)

Lactobacillus rhamnosus 10 billion, Lactobacillus reuteri 10 billion, Lactobacillus acidophilus 3 billion,

Lactobacillus plantarum 3 billion, Bifidobacterium lactis 3 billion, Bifidobacterium breve 3 billion, Bifidobacterium

longum 3 billion

Florajen (1 capsule=460 mg) Acidophilus > 20 billion

Ultraflora Women’s Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RI-14

UltraFlora Spectrum (Serving Size: 1 Cup); bottle: $41.25

Saccharomyces boulardi, Bifidobacterium lactis (Bi-07), Lactobacillus plantarum (Lp-115), Lactobacillus salivarius (Ls-33), Lactobacillus acidophilus (NCFM), Streptococcus thermophiles (St-21), and Bifidobacterium lactis (Bi-04)

UltraFlora 1B (1 Bottle: $57.75) Lactobacillus acidophilus NCFM ~30 billion, Bifidobacterium lactis (Bi-07) ~30 billion

Definitions & Facts• “Gut”- refers to intestines when referring to body in biomedical language,

although sometimes may be referring to whole digestive tract• GALT (Gut-Associated Lymphoid Tissue)- the largest part of the immune

system in the body; the large intestine is a part of this system• Stomach (Sterile)--- small intestine (bacteria present)--- large intestine

(more bacteria present, and are usually anaerobic bacteria)• pH of stomach= 1.5-3.5, pH of small intestine= 6-7.4, pH of large intestine=

5.5-7• In general, “bad bacteria” (pathogenic bacteria) prefer a pH closer to 7

(though may range from 4.6-7.0)• There is no particular recommended percentage of how much intestinal

bacteria should be “good” vs. “bad”• Some of the “good” bacteria are lactic acid producing (i.e., lactobacillus)

Picture of Immune System & GALT

https://www.aids.gov/images/aids-infographics/immune-system101-2-1.jpg http://www.integrativepsychiatry.net/_uploaded_files/galt.png

Definitions & Facts• The stomach could kill off bacteria, but bacteria may not sit in the stomach for a

long period of time and if keep filling diet with “bad bacteria” then may be pushing those “bad bacteria” to colonize in large intestine• Bacteria particularly inhabit the large intestine• Definition for Customer and Employee Purposes• Probiotic- means “good” or supportive bacteria • Prebiotic- a source of nourishment (usually fiber) for bacteria that already

exist• Are probiotics dead bacteria? No probiotics are living bacteria.• Aggregation is a desired property of probiotics, because it allows the probiotics

to interact with the “bad” bacteria

Sources of Probiotics/Prebiotics for Human Consumption

• Food Sources of Probiotics• Yogurt, Sauerkraut (unpasteurized), Miso soup, Soft Cheeses, Kefir, Sourdough

Bread, Milk Containing Probiotics, Sour pickles (no vinegar in process), Tempeh

• Food Sources of Prebiotics• Asparagus, Jerusalem artichokes, bananas, oatmeal, redwine, honey, maple

syrup, and legumes

• Probiotics that are produced by manufacturers• Prebiotics that are produced by manufacturers

Frequently Asked Questions (FAQs)• Where do probiotics work?

• Particularly in the small and large intestines

• How many probiotics are needed to make a significant difference in the number of good bacteria? There is no definitive answer to this, though usually seems to be 10^6-10^9 cfu/mg/day (lower dose for small intestine and higher dose in the large intestine)• When do you need a higher dose of probiotic? For more acute infections such

as diarrhea• Will the probiotics reach the site of action?• Do probiotics create an environment easier for “good bacteria” to grow or do

they just “add” good bacteria to the gut?

Frequently Asked Questions (FAQs)• Enteric coating of Probiotics?• Why is it good to take probiotics even if not currently on antibiotics?• More “good” bacteria already in intestines and digestive system before taking

antibiotic

• What if the patient is immuno-deficient? Controversial, but “good bacteria” are needed to balance out the “good” vs. “bad” bacteria, and play a role in activating the immune system; however, if severely immunocompromised, American Family Physicians do not recommend it, although they also say it is effective• Adverse effects: Flatulence, and rarely sepsis

Benefits of Probiotics at the Cellular Level

• There needs to an appropriate balance of “good” vs. “bad” bacteria; exact balance not calculated

• “Good bacteria” help make Vitamin K• Help digest food • Can stimulate the production of Peripheral Blood Mononuclear cells

• Regulatory T cells• Specific uses for specific strains• Gut bacteria produce some neurotransmitters: Serotonin, dopamine, and GABA• Help strengthen linings of the digestive system• It is speculated that the bad bacteria learn to feed off “fast foods,” while good

bacteria “like” to feed off of sources already mentioned, and this is part of cravings

Importance of Fiber• Fiber is what prebiotics are made of• If do not have enough fiber, then the “bad bacteria” can sit in the

intestine which allows them to multiply in your intestine over time• Fiber feeds the probiotics (good bacteria)• Suggest that patient eat diet high in fiber or take pre-biotic• Generally recommended to take in at least 25 grams of fiber per day with

water • Soluble• Insoluble

• In general, many bad bacteria feed off of sugar

General Characteristics of Effective Bacterial Strains

• Has demonstrated safety & efficacy; none of the usual renal or hepatic adjustments• Resistance to acid, bile, pepsin, and pancreatin• Adherence to the GI epithelial tissue• Ability to store bacteria• May enhance immune response by stimulating cytokines to come to

infected site• If lactic acid bacteria this is generally good characteristic• If has strains of pathogenic bacteria it targets, this is good characteristic

Mechanisms of Action of Saccharomyces boulardi

• Saccharomyces works by binding to glycoprotein receptor site (and ingesting it) for Toxin A at intestinal brush border

http://8b7a91801591cac4b290-abbac3ca2ecec271a197a4cd05b43329.r61.cf3.rackcdn.com/saccharomyces-boulardii-purple.jpg

Importance of Different Bacterial Strains Contained in Probiotics

• NCFM (North Carolina Food Microbiology; isolated at NC State in the 1970s); strain of Lactobacillus acidophilus: • Gram (+); found in intestine, mouth, and vagina; also found in kefir; has

excellent tolerance to acid, bile salt, and pancreatin, and very good resistance to pepsin; has very good adherence to epithelial cell lines


• HEAL-9 (Lactobacillus plantarum):• Effective in reducing the risk of the common cold

• Lpc-37 (Lactobacillus paracasei):• Gram (+); has excellent acid tolerance and excellent pancreatin

resistance; has fair bile salt tolerance and fair pepsin tolerance; has excellent adhesion to epithelial cell lines; has excellent inhibition of salmonella typhimurium, staphylococcus aureus, Escherichia coli, and good inhibition of Listeria monocytogenes; produces only L(+) Lactic acid; improves immune response as related to cytokine IL-12 (improves more than L. plantarum); in a 5-strain formula restored the good bacteria in the GI


• 8700-2 (Lactobacillus paracasei):• Effective in reducing the risk of the common cold

• GR-1 (Lactobacillus rhamnosus):• Prevents adhesion from “bad” bacteria and adhere to cells of vagina,

bladder, and intestine; due to acid production has antiviral properties (i.e., can destroy HIV); has anti-inflammatory effect

• RC-14 (Lactobacillus reuteri): • Prevents adhesion from “bad” bacteria and adhere to cells of vagina,

bladder, and intestine; due to acid production has antiviral properties (i.e., can destroy HIV); may prevent surgical infections, particularly caused by Staph Aureus


• Ls-33 (Lactobacillus salivarius):• Gram (+); has excellent acid tolerance, excellent bile salt tolerance, excellent

pancreatin tolerance, and very good pepsin tolerance; has overall excellent adherence to epithelial cells; manufactures only L(+)-Lactic acid; improves immune response as related to IL-10 (when compared to Lc lactis), and stimulates IL-12 more than E. coli; has excellent activity against Staphylococcus aureus, very good activity against Escherichia coli, and good activity against Listeria monocytogenes and Salmonella typhimurium; anti-inflammatory properties (animal studies)

• Bi-07 (Bifidobacterium lactis):• Helps reduce bloating in patients with bowel disorders

• HN-019 (Bifidobacterium lactis):• May decrease infant diarrhea caused by E. Coli or rotavirus


• Lp-115 (Lactobacillus plantarum):• may increase the lactic acid in the gut to kill the “bad” bacteria; great at degrading oxalate

(better than other strains of lactobacillus); Lactobacillus 115 has good activity compared to other strains in inducing the secretion of IL-10 & IL-12; may help increase immune function so patient can more easily receive vaccine; easily survives in the GI, because has high tolerance to acid, bile, pepsin, and pancreatin; easily adheres to the intestinal mucosa which means it is close to the intestinal immune system, which may affect the immune response more and also keeps the “bad” bacteria from colonizing in the intestine

• St-21 (Streptococcus thermophiles):• Does not “like” being outside of the refrigerator


• Bi-04 (Bifidobacterium lactis):• Gram (+); survives in the GI, because has tolerance to acidic

conditions and bile; has very good adherence to human epithelial tissue; produces L(+)- lactic acid; rapidly restores bacteria after antibiotic treatment; stimulates the immune system (IgG induction)

What to Say to Customer Regarding Probiotics

• Cost: Saccharomyces boulardi: $8 for 14 count bottle; other prices listed previously• “The saccharomyces probiotic can be used in any age of children though

sprinkling it on food is probably best for infants. It is a probiotic that is designed to be taken with the antibiotic. Most of the bacteria in the body are located near the intestines, and most of the immune system is located near the intestines. So it is important to keep the bacteria in the intestines healthy. A healthy diet is also important, because feeding the good bacteria is crucial to keep a healthy balance in the digestive system. “Bad” bacteria feed off of glucose. Good bacteria also help assemble neurotransmitters such as serotonin, dopamine, and GABA. This can affect your mood.”

Studies: Results Summarized• One review article indicated that the studies for the use of probiotics to

prevent Antibiotic Associated Diarrhea showed good data, but were not powered (did not have enough people to show that the probiotics had a favorable outcome on a rare condition). Because there are so many different probiotics, because the probiotics used in the studies differ, and because Antibiotic Associated Diarrhea is not a very common condition, it makes it harder to conduct clinical trials. However, there also seems to be little evidence that probiotics have any significant adverse effects. Also, it is very difficult to quantify the favorable long-term effects of probiotics, because they have been a product for only a short time. As the review article mentioned, it is not known which populations except those taking antibiotics have the most need for probiotics.”

What to Say to Provider Regarding Probiotics

• “It is good to recommend probiotics to your patient, because your GI tract is next to 70% of the body’s immune tissue and the GI tract also produces neurotransmitters as well which can affect cognitive functioning. Studies have shown that probiotics have benefit in patients, but it is difficult to find patients for these studies, because Antibiotic Associated Diarrhea is reported as a rare condition (probably because it is difficult to measure this in the outpatient setting). Even if patients are not likely to develop antibiotic associated diarrhea (which is what the saccharomyces would be used for), it is better that patients take probiotics for their long-term health since the GI system seems to be connected to so many different organ systems in the body.”

Risk of Each Statin Causing Myopathy

High Risk of Myopathy Statins (Most Concern)

Intermediate to Low Risk of Myopathy

Low Risk of Myopathy

Lovastatin (Mevacor, Altoprev)

Rosuvastatin (Crestor)

Pravastatin (Pravachol)

Simvastatin (Zocor)

Fluvastatin (Lescol)

Atorvastatin (Lipitor)

Pitavastatin (Livalo) (Newer, so

more data possibly needed)

Reason Some Statins At Higher Risk of Causing Myopathy

• Thought that hydrophilic (“water-loving”) statins such as pravastatin, rosuvastatin, and fluvastatin are less likely to cause myopathy, because theoretically they would not cross the muscle tissue as easily as hydrophilic (“fat-loving”) statins• Lipophilic statins (“fat-loving”) include lovastatin,

simvastatin, and atorvastatin• However, this isn’t well-documented in the literature and

more of a theoretical mechanism

Mechanism of How Statins Work • Statins work by lowering HMG-CoA reductase (an

enzyme) which reduces the production of the mevalonic acid; lower mevalonic acid causes an increased expression of LDL receptors on the liver, which then removes LDL from the circulation• The enzyme HMG-CoA reductase is also used for the

synthesis of Co-enzyme Q10

Mechanism of How Statins Deplete CoQ10 & Importance of CoQ10

• CoQ10 is part of the electron transport chain which produces 34/36 body’s ATP (rest of ATP produced from Krebs Cycle)• CoQ10 is also known as Ubiquinone• ATP are needed for synthesis and transport of macromolecules (i.e.,

proteins)• Found in highest quantity in mitochondria of high-energy organs

(i.e., heart)• The recommended amount of CoQ10 per day at Dilworth Drug &

Wellness Center is 100 mg of CoQ10 for every pill the patient is taking

Mechanism of How Statins Deplete CoQ10 & Importance of CoQ10

• CoQ10 is a large molecule that reportedly resembles a vitamin, is fat soluble (easily crosses cell membranes), is an antioxidant (helping produce Vitamins C & E)• Possible Adverse of effects of CoQ10 include: Diarrhea, increased liver

function tests, and loss of appetite• Never want to give too high a dose of antioxidants, because more

likely to cause cancer; also oncologists often will not give antioxidants, because they believe can contribute to tumor growth• Note: If taking Red Yeast Rice would still want to take CoQ10; also

may find CoQ10 in Cold water fish, beef, and chicken

Structure of CoQ10

http://my-lifespan.com/img/coenzymeq10_structure.jpg

Structure of Vitamin K

http://www.omjournal.org/images/images%20052014/R_vitk-f1.jpg

Importance of the Mitochondria• What is a mitochondria? An organelle within a cell that breaks down

nutrients into ATP• ATP (Adenosine Triphosphate) is needed for muscles to contract,

endocytosis and exocytosis, and other cellular functions such as the synthesis of RNA and DNA• Mitochondria per human cell: 1,000-2,000 • Mitochondria are especially prevalent in high energy areas such as the

heart and brain• Heart cells have a very low capability for regeneration; controversial

as to whether brain cells have capability for regeneration, but would not want to damage

Mitochondria

http://www.macroevolution.net/mtdna-human-chimpanzee.html

Picture of Electron Transport Chain

http://www.ims2000.org/images/coenzyme-q10-natural-wealth-3092.jpg

Myopathy• Proposed Mechanism of Myopathy• If not enough CoQ10 may limit the ability of the mitochondria to

produce energy, and disturb cellular respiration• If cellular respiration is disturbed this may lead to a “back-up” of

substances in the cell• Some of the harmful products may include lactic acid and oxygen (the

lack of oxygen leading to formation of free radicals)• If not enough CoQ10 which is an antioxidant may also lead to build up of

free radicals in the muscle cells• More likely happens in muscle than in fat cells, because muscle cells

require a lot of mitochondria and ATP, and if those products are not being produced it leads to a “back-up” of the substances in the cell that may cause myopathy

Statin Nutrient Depletion Treatment• Co-enzyme Q10 (commonly referred to as CoQ10)• Naturally made in the human body• Antioxidant • Very lengthy process to synthesize

• Found in highest quantity in high-energy organs (i.e., heart, brain)• Important to have Quality Product

• Lipophilic• Crystal Forms (not preferred)• Large Molecule

• Is it ok to take Co-enzyme Q10 with warfarin? Studies• What other Uses Does CoQ10 have? May help treat diastolic heart failure, high blood

pressure, Parkinson’s Disease, Huntington’s Disease, gum disease, diabetes, and anthracycline cardio-induced toxicity (systolic)

What to Say to Customer Regarding CoQ10

• Cost:• Dilworth Drug & Wellness Center 100 mg $19.90• Dilworth Drug & Wellness Center 400 mg $39.90

• “CoQ10 is found in almost every organ in your body, though it is especially found in your heart and brain, so it may help raise energy levels in the human body. It’s main indication is if you are taking a statin to prevent muscle pain, but it may also be used to help to lower blood pressure and for treating heart failure. It may also provide some benefit to immune function (make specific to patient’s most needed indication). If taking warfarin would recommend letting physician know before taking CoQ10. It has been said there are some case reports out there that CoQ10 could make INR (how fast your blood clots) increase (meaning it doesn’t clot as fast, which is what warfarin is supposed to do. However, it would seem more believable that if it did anything it would make the INR decrease (not clot as fast), because CoQ10 is similar in structure to Vitamin K, which is actually used as an agent to stop warfarin from thinning the blood. To help CoQ10 absorb better it should be taken with food.”

Other Points About CoQ10 & Statins• Take CoQ10 with meal (especially fatty meal, because CoQ10 is fat soluble,

meaning it will be absorbed more easily if ingested with fat); makes sense because has a very similar structure to the fat soluble vitamin, Vitamin K• Absorption increased when taking with food: Lovastatin• Absorption decreased when taken with food: Pravastatin, Fluvastatin,

Atorvastatin• Doesn’t matter if taken with food or not: Simvastatin, Rosuvastatin• Statins that should be taken at bedtime: Fluvastatin, Lovastatin, Simvastatin • Cholesterol produced most during fasting states (often nighttime is longest

fasting state for many people)

Studies: Results Summarized• One Meta-Analysis with data conducted (up to the year 2015) found that statins do

significantly decrease the amount of CoQ10• Lipophilic and hydrophilic statins reduced the amount of CoQ10 in the body the same

amount• In a case report, one 72-year-old female was treated with both warfarin and CoQ10;

the results showed that she experienced a reduced amount of effect from warfarin (lower INR: International Normalized Ratio- to the patient would say lower INR means blood clots faster than higher INR which means blood clots slower); did not report what dose of CoQ10 or the Therapeutic Range of Warfarin in the study

• In a randomized double blind placebo controlled cross-over trial, the study results found that the CoQ10 nor the Ginkgo biloba moved the INR of the patients out of the therapeutic range (INR: 2-4); included patients with mean age of 64; only included 24 patients and confidence intervals were very large; opinion: not a very good study

What to Say to Provider Regarding CoQ10

• “Studies show that statins significantly deplete CoQ10. I would caution giving it to a patient who is taking warfarin, though it is unlikely to increase INR, although it may decrease it. It is similar to Vitamin K in structure. It may have a lot of other benefits such as lowering blood pressure as well. Do not recommend crystallized CoQ10, because it is not absorbed well in the intestines.”

Metformin• Note: Diabetics may already be pre-disposed to have a low level of Vitamin B12 • Very effective at reducing Hemoglobin A1C (a measure of glycated hemoglobin; usually

measured every 3 months)• A1C goals: For most adults <7.0%, though elderly may have a higher A1C goal(varies

depending on which guidelines are used)• The recommended daily intake of Vitamin B12 is ranges from 0.4-2.8 mcg/day• Some diabetics may not be aware their product has metformin in it if they are on a

brand-name or combination product• Other Causes of Vitamin B12 Deficiency: Dietary, Inhibition of Absorption (i.e. Crohn’s

Disease, Celiac Disease), PPIs/H2RAs > 2 years, and Alcoholism• Note: Brain’s only fuel is glucose; nothing but glucose (no other types of sugar, protein,

or fats) are used for energy supplies in the brain

Medications With MetforminGlucophage (Metformin) Glucovance (Glyburide/Metformin)

Glumetza (Metformin) Jentadueto, Jentadueto XR (Linagliptin/Metformin)

Fortamet (Metformin) ActoPlus Met, ActoPlus Met XR (Metformin/Pioglitazone)

Glucophage XR (Metformin) PrandiMet (Metformin/Repaglinide)Kazano (Alogliptin/Metformin) Avandamet (Metformin/Rosiglitazone)

Invokamet (Canagliflozin/Metformin) Kombiglyze XR (Metformin/Saxagliptin)Xigduo (Dapagliflozin/Metformin) Janumet, Janumet XR (Metformin/Sitagliptin)

Synjardy (Empagliflozin/Metformin)Metaglip (Glipizide/Metformin)

Importance of Vitamin B12 (Cyanocobalamin, Cobalamin)

• Vitamin B12 is a water soluble vitamin, meaning that if patients take in an excess of this vitamin there is little risk of toxicity, because it is excreted through the kidneys• Consequence: Because water soluble vitamins are not stored easily,

humans need to continuously take in water soluble vitamins such as Vitamin B12

• How is Vitamin B12 different from the other B Vitamin? Liver stores ~90% of Vitamin B12 content (stores will last up to 5 years); cobalt is contained in B12• Deficiency possibly caused by decreased calcium absorption due to

metformin which is needed to absorb Vitamin B12 at the terminal ileum• Calcium supplementation may help if patient suffering from B12

absorption

Vitamin B12 Levels

High (>900) pg/mLNormal 300-900 pg/mL

Lower Normal/Low 150-300 pg/mLLow <150 pg/mL

Importance of Vitamin B12• Vitamin B12 Deficiency Can Lead To the Following: Neuropathy,

Reduced Cognitive Functioning, lesions of the GI, and Anemia (Megaloblastic if due to Vitamin B12 deficiency; size too large to move from bone marrow, because RBCs did not divide normally and are too large); need Red Blood Cells to carry oxygen to organs • Vitamin B12 Functions: Helps Red Blood Cells B/C Need Vitamin B12

as a nutrient to mature, Helps Protect Nerves (Myelin)• Dietary sources of Vitamin B12: Meat, Eggs, Cheese; Beef Liver, Clams• Vegans at increased risk of deficiency

More on Vitamin B12• Vitamin B12 Deficiency may also mimic Neuropathy which is common in diabetics• Proton Pump Inhibitor (and use of H2RAs) use > 2 years may also cause Vitamin B12

Deficiency• Adequate serum blood level of Vitamin B12 does not mean have adequate tissue

levels of Vitamin B12• Possible Mechanism of Depletion: Metformin causes malabsorption of cobalamin

from food at the distal ileum (30%); for PPIs & H2RAs may be because they reduce stomach acid (hydrochloric acid) which removes the Vitamin B12 from food• Adverse of Effects High Vitamin B12: Levels > 900 pg/mL cause bone cell

proliferating disorders (rarely), liver injury (rarely), and kidney injury (rarely); people with higher than normal B12 levels are asymptomatic; would be difficult to build up toxic levels of B12 because Vitamin B is water soluble, though it is possible if taking in really high amounts of B12

More on Vitamin B12• Thought that absorbed better sublingually, because absorbs more directly into blood and

bypasses digestion; large doses of B12 may bypass the usual digestive mechanisms (meaning it can be more easily absorbed if taken in large doses than in small doses)

• Factors affecting B12 Absorption: stomach needs to produce low pH, intrinsic factor, pancreatic function (Exocrine: digestion of food), and absorption of food in the stomach• Liposomal form more easily absorbed, because Vitamin B12 is water soluble; the fat-

soluble “carries” the water-soluble part to the ileum (small intestine) where it is absorbed

• Vitamin B12 is not synthesized by humans except in the large intestine where it is not absorbed

• Elderly patients stop making stomach acid which leads to decreased absorption of Vitamin B12

• 1.5-15% of the population is estimated to have a Vitamin B12 deficiency• Interesting Fact: Can be used to treat cyanide poisoning (dose unclear)

Examples of Customers Who May Need Vitamin B12 Even Though Not

on Metformin• Elderly Patients• Anemic Patients• Patients with liver dysfunction (i.e., alcoholism)• People with bowel dysfunction and disease (i.e., Crohn’s Disease and Celiac Disease)• Other Medications (i.e., PPIs, H2RAs)• Patients with diabetes; patients experiencing neuropathy• Patients who are elderly, because Vitamin B12 deficiency could be contributing to or

causing Alzheimer’s type symptoms• Pregnant patients• Patients who do not eat meat

What to Say to Customer Regarding Vitamin B12

• Cost:• Dilworth Drug & Wellness Center Vitamin B12 (Methylcobalamin & Hydrocobalamin Liposomal) 2

fl. oz. (60 mL): $24.90

• “Vitamin B12 is needed to protect nerves, and blood cells. Vitamin B12 is definitely needed for people who have Vitamin B12 Deficiency, and all diabetics, even those not on metformin. A vitamin B12 Deficiency itself can lead to neuropathy, and to symptoms that may look like dementia. Just because blood levels are normal does not mean that tissue levels are normal. It is also critical to take Vitamin B12 if you are a heavy drinker or have anemia. Because of the neuropathy, Vitamin B12 deficiency can lead to cognitive disorders. Vitamin B12 is a water soluble vitamin excreted by the kidneys and it’s rare that toxic levels of it build up in the body. Vitamin B12 may also reduce homocysteine which is linked to increased risk of MI and stroke. The Dilworth Liposomal form of Vitamin B12 is great to take, because it is hard to absorb Vitamin B12 anyway, but the liposomal form helps the Vitamin B12 reach the small intestine for optimal absorption.”

Studies: Results Summarized• In Type II Diabetics, Metformin showed to reduce Vitamin B12 levels compared to those who were not

taking Metformin• There is a decrease in Vitamin B12 levels and folic acid in those who have been using Metformin short-

term• One cross-sectional study with 203 type 2 diabetic patients showed that the longer the patients had

diabetes the more chance patients had of having a Vitamin B12 deficiency; the study also showed that patients who took a multivitamin were statistically significantly less likely to have a Vitamin B12 deficiency; also, there was no statistically significant difference in incidence of B12 deficiency in diabetics who were taking metformin and those were not currently using metformin (meaning diabetics taking or not taking metformin may have a Vitamin B12 deficiency), although patients taking metformin had lower B12 levels and were at higher risk of B12 deficiency; researchers said that when serum blood levels fell below <350 pg/mL that patients were more likely to have a tissue deficiency of Vitamin B12 even though they had no serum deficiency; patients who had B12 levels of 100-350 and had methylmalonic acid levels >243 nmol/L or homocysteine >11.9 nmol/L were considered to have Vitamin B12 deficiency

• One retrospective study of 259 elderly patients, found that patients who had Vitamin B12 deficiency were also more likely to have cognitive decline; there was a higher rate of cognitive decline in patients who had dyslipidemia in addition to the Vitamin B12 deficiency

What to Say to Provider Regarding Vitamin B12

• “I would suggest probably screening patients for B12 deficiency if they are diabetic, because the prevalence of B12 deficiency is significantly higher in those who are diabetic vs. those who are not. In has been proven statistically that diabetics taking metformin are at higher risk of developing B12 deficiency and have lower B12 levels, but they still do not have a higher prevalence of B12 deficiency than those diabetics not taking metformin. B12 deficiency may also contribute to what may seem to be psychological disorders.”

Proton Pump InhibitorsProton Pump Inhibitors

Omeprazole (Prilosec, Prilosec OTC)Lansoprazole (Prevacid, Prevacid 24 hour)

Dexlansoprazole (Dexilent, Kapidex)Rabeprazole (Aciphex)

Pantoprazole (Protonix)Esomeprazole (Nexium)

Rapid Release Form Omeprazole (Zegarid)

Histamine-2 Receptor Antagonists (H2RAs)

Ranitidine (Zantac, Select)Cimetidine (Tagamet); avoid in the elderly

because of possible confusion, and metabolized by the liver

Nizatidine (Axid)Famotidine (Pepcid, Fluxid, Select)

Other Drugs that May Lead to Magnesium Depletion

Diuretics (Loop and Thiazide)Aminoglycosides (Amikacin, Gentamicin, Tobramycin)

AmphotercinCisplatin

CyclosporinePentamideFoscarnet

Common Drugs that Deplete Potassium

• If potassium in deficient state, then magnesium will not allow the potassium to be corrected• Hypokalemia (too little potassium) or Hyperkalemia (too much potassium

can cause arrhythmias • Diuretics, Methylxanthines (i.e., caffeine), Penicillins, Quetiapine,

Amphotercin B, Gentamicin, Cisplatin, Epinephrine and Other Beta Agonists• Recommended Daily Intake of Potassium ranges from 3,000 mg/day to

5,100 mg/day depending on age• What other foods besides bananas have potassium?: Spinach (cooked),

sweet potato, cooked broccoli

GERD (Gastroesophageal Reflux Disease)

• PPIs in the outpatient setting are most commonly used to treat Gastroesophageal Reflux Disease (GERD)• Mechanism of GERD:

https://static1.squarespace.com/static/517d1f3ee4b02921d70b3783/t/528d58bbe4b04fc308321b94/1384995006130/Reflux+mechanism.png

Mechanism of Action of PPIs & H2RAs

https://cme.dannemiller.com/media/articles/429/Figure-5.pnghttp://www.nps.org.au/__data/assets/image/0004/299182/PPI-pharmacology.png

Theoretical Mechanisms of PPIs Depletion of Magnesium

• Theoretical Mechanism PPIs: PPIs possibly could be causing the intestines to not absorb magnesium well; PPIs could be causing magnesium depletion, because it is commonly thought when patients stop PPIs it may help replete magnesium.

Proton Pump Inhibitors Nutrient Depletions

• If on an OTC proton pump inhibitor then do still need repletion?• What if they are on an H2RA or antacids?• Proton Pump Inhibitors may deplete Magnesium and Calcium• Unfavorable Effects of PPIs on Micronutrients:

• Lowers Calcium-----Fractures (Elderly already at risk)• Vitamin B12 Deficiency (being treated > 3 years)-- Neuropathy

• Other Consequences of Taking PPIs:• C. difficile Associated Diarrhea• Aspiration Pneumonia

• For Gastroesophageal Reflux Disease, patient should be on PPI for 4-8 weeks and H2RA for 6-12 weeks with lifestyle modifications in addition

Importance of Magnesium• Why is Magnesium Oxide not ideal for a patient?• 50-60% of Magnesium is stored in the bone, with ~40% being

stored in soft tissues (i.e., muscles and organs), and <1% being in the blood• The amount of Magnesium in the body is regulated by the

kidneys• Magnesium is used as a cofactor for many reactions in the body• Normal Intake of Magnesium is 300-360 mg/day; generally

calcium is 1,000 mg/day to 1,250 mg/day for premenopausal women and 1,500 mg/day for postmenopausal women

Importance of Magnesium• Passive Paracellular Non-Saturable Pathway (80-90%) responsible for

intestinal uptake• Active Transcellular Pathway (10-20%) responsible for intestinal uptake• Magnesium and Calcium are cations• Depletion: Seizures, tremors, involuntary muscle contractions, QT

prolongation, and arrhythmias• Functions: Protein synthesis, muscle function, nerve function,

regulation of blood glucose, and regulation of blood pressure; helps prevent osteoporosis and migraine headaches

Importance of Calcium• 99% of calcium in the body is stored in the bones• Also used for muscle contraction, neurotransmitter release, blood

clotting and cell signaling• Adverse Effects of High Calcium (Hypercalcemia): Digestive issues (i.e.,

constipation), increased urination, weak muscle and bones, and increased thirst (higher percentage of calcium and less water in the blood)• Food with calcium: Milk, Cheese, Yogurt, Orange Juice, Dark Greens

like Spinach and Collard Greens

Why Magnesium Bisglycinate and Magnesium Malate?

• Bisglycinate has two bisglycinate molecules, which makes it very absorbable as the glycine inhibits the magnesium from binding to phytates, and is said to cross the blood brain barrier which is good for emotional and psychological disorders; chelate means the magnesium has an amino acid (in this case glycine) attached to it; magnesium is oxide is beneficial because it can help improve absorption of other drugs, and may have stool softening properties• Malate is part of the Krebs Cycle, so when given with malic acid with

magnesium this helps the Krebs Cycle continue to cycle, which may reduce backload of substances like lactic acid and produces ATP

Krebs Cycle

http://static.trunity.net/files/150501_150600/150528/thumbs/krebs_438x0_scale.gif

GI Tract Absorption of Magnesium

http://www.albionminerals.com/human-nutrition/magnesium-white-paper

Comparison of Different Magnesium ProductsCharacteristics Magnesium Bisglycinate

(Magnesium Glycinate)Magnesium Malate

Magnesium Deficiency (Best Choice)

X

Muscle Pain, Fatigue (Best Choice)

X

Better at Getting Rid of Lactic Acid (Best Choice)

X

Less Diarrhea (Theoretically) (Best Choice)

X

Best Bioavailablility (Best Choice)

X

More Thoughts• Need healthy GI tract to absorb Magnesium, especially healthy

bacteria in the ileum (small intestine)• Calcium citrate may be the best calcium to take, because even if acid

production is suppressed (i.e. if taking PPI), it still doesn’t need acid to be absorbed, because citrate is a derivative of citric acid• Calcium carbonate contains the most elemental calcium (~40%), but

calcium citrate has better absorption • Separate Magnesium and/or Calcium by 2 hours from

Fluoroquinolones & Tetracyclines due to chelation; reduces the levels of the antibiotics; so if taking antacid would separate by 2 hours

More Thoughts•Magnesium Malate binds Aluminum in the body• Necessary to have Magnesium oxide to help absorb other

medications and also increases absorption of Magnesium Bisglycinate• Advise patient to eliminate caffeine in diet (perhaps could

keep a list of foods and beverages with caffeine in them)

What to Say to Customer Regarding Magnesium

• Cost: • Dilworth Drug & Wellness Mg Malate 90 ct: $19.90• Dilworth Drug & Wellness Mg Bisglycinate 90 ct: $25.90

• “Magnesium is often depleted when taking acid reducing medications and this can have serious side effects. If you don’t get enough magnesium, your muscles can hurt and you can feel a lack of energy. Also, a lack of magnesium can keep low potassium from correcting. Magnesium Bisglycinate is better for correcting a magnesium deficiency and causes less diarrhea, while Magnesium Malate is better for relieving muscle soreness, fatigue, and getting rid of lactic acid.”

Studies: Results Summarized• PPIs are associated with causing hypomagnesemia when used for >3

months, although many of the authors studies show there is no causation associated with hypomagnesemia. However, a recent meta-analysis showed that there is an increased risk of hypomagnesemia when taking PPIs, though more homogeneous studies are needed.

What to Say to Provider Regarding Magnesium & Calcium

• “Both Calcium and Magnesium are very important to the body. Depleting Calcium can cause fractures and depleting magnesium can lead to arrhythmias. Some data have shown that patients who take PPIs and/or H2RAs are at risk of depleting Magnesium and/or Calcium. I would suggest checking the Calcium and Magnesium levels in patients taking these drugs, and it would be a good idea to supplement especially with magnesium in these patients, because of the extreme side effects of magnesium depletion. Magnesium Bisglycinate is better for absorption and not causing diarrhea, but Magnesium Malate is better for those patients feeling fatigued, because malate is part of the Krebs Cycle and the extra malate helps generate the Krebs Cycle.”

Oral Contraceptives: MonophasicMonophasic

Alesse (Levonorgestrel/Ethinyl Estradiol) Levlen (Levonorgestrel/Ethinyl Estradiol)

Apri (Desogestrel/Ethinyl Estradiol) Levora (Levonorgestrel/Ethinyl Estradiol)

Aviane (Levonorgestrel/Ethinyl Estradiol) Loestrin (Norethindrone acetate/Ethinyl Estradiol)

Brevicon (Norethindrone/Ethinyl Estradiol)

Lo-Ovral, Ovral (Norgestrel/Ethinyl Estradiol)

Demulen (Ethynodiol diacetate/Ethinyl Estradiol)

Lo-Ogestrel, Ogestrel (Norgestrel/Ethinyl Estradiol)

Genora 1/35 (Norethindrone/Ethinyl Estradiol)

Microgestin, Microgestin FE (Norethindrone acetate/Ethinyl Estradiol)

Genora 1/50 (Norethindrone/Mestranol) Modicon (Norethindrone acetate/Ethinyl Estradiol)

Levlite (Levonorgestrel/Ethinyl Estradiol) MonoNessa (Norgestimate/Ethinyl Estradiol)

Oral Contraceptives: MonophasicMonophasic

Necon (Norethindrone/Ethinyl Estradiol) Ovocon (Norethindrone/Ethinyl Estradiol)

Nordette (Levonorgestrel/Ethinyl Estradiol) Ovranette (Levonorgestrel/Ethinyl Estradiol)

Norinyl 1/50 (Norethindrone/Mestranol) Portia (Levonorgestrel/Ethinyl Estradiol)

Norinyl 1/35 (Norethindrone/Ethinyl Estradiol) Sprintec (Norgestimate/Ethinyl Estradiol)

Nortrel (Norethindrone/Ethinyl Estradiol) Tri-Norinyl (Norethindrone/Ethinyl Estradiol)

Ortho-Cept (Desogestrel/Ethinyl Estradiol) Yasmin (Drospirenone/Ethinyl Estradiol)

Ortho-Novum 1/35 (Norethindrone/ Ethinyl Estradiol)

Yaz (Drospirenone/Ethinyl Estradiol)

Ortho-Cyclen (Norgest Zovia (Ethynodiol Diacetate/Ethinyl Estradiol)

Oral Contraceptives BiphasicBiphasic

Aranelle (Norethindrone/Ethinyl Estradiol)

Necon (Norethindrone/Ethinyl Estradiol)

Jenest (Norethindrone/Ethinyl Estradiol)

Ortho-Novum (Norethindrone/Ethinyl Estradiol)

Mircette (Desogestrel/Ethinyl Estradiol)

Nelova (Norethindrone/Ethinyl Estradiol)

Oral Contraceptives: TriphasicTriphasic

Enpresse (Levonorgestrel/Ethinyl Estradiol) Tri-Levlen (Levonorgestrel/Ethinyl Estradiol)Estrostep FE (Norethindrone Acetate/Ethinyl

Estradiol)TriNessa (Norgestimate/Ethinyl Estradiol)

Necon (Norethindrone/Ethinyl Estradiol) TriNorinyl (Norethindrone/Ethinyl Estradiol)Nortrel (Norethindrone/Ethinyl Estradiol) TriPhasil (Levonorgestrel/Ethinyl Estradiol)

Ortho Tricyclen (Norgestimate/Ethinyl Estradiol)

Tri-Sprintec (Norgestimate/Ethinyl Estradiol)

Ortho Tricyclen Lo (Norgestimate/Ethinyl Estradiol)

Trivora (Levonorgestrel/Ethinyl Estradiol)

Ortho-Novum (Norethindrone/Ethinyl Estradiol)

Velivet (Desogestrel/Ethinyl Estradiol)

Oral Contraceptives: QuadraphasicQuadraphasic

Natazia (Dienogest/Estradiol)

Oral Contraceptives Drug Nutrient Depletions

• Probiotics, Magnesium, Zinc, any B Vitamin (including B2, B6, B12, and folic acid), Vitamin C, Vitamin E, and Selenium

• Zinc is an important cofactor for many reactions in the body and may be taken prophylactically to prevent colds

• Important that mother treat these depletions for herself and in case she were to become pregnant, because babies need all of these substances

• Infant receives its first probiotics from its mother after birth• Theoretical Mechanism: Could be that the liver needs too many of these vitamins to

metabolize the active ingredients in most birth control pills; also may be because causes bleeding, and that both Vitamins B and C are both water-soluble vitamins (meaning if there is bleeding, and because blood has a high percentage of water in it that because these vitamins dissolve in water there could be a low level of these vitamins in the blood, because these vitamins are leaving the blood through bleeding)

What to Say to Customer Regarding Depleted Nutrients When Given Oral

Contraceptives• Cost: DD&WC Women’s Multivitamin $25.99• “Oral Contraceptives can deplete nutrients, and especially if taken

over a long period of time. It is best to take a multivitamin to help supplement the vitamins and minerals that these deplete.”

Studies: Results Summarized• Oral contraceptives may decrease the amount of nutrients that are

absorbed. One review stated that because certain nutrients are depleted that women should supplement with those nutrients, because not only may the contraceptives be depleting the nutrients, but the woman additionally may have poor diet and/or absorption.

What to Say to Provider Regarding Depleted Nutrients When Given Oral

Contraceptives• “Studies show that patients lose a lot of nutrients when taking contraceptives, so it is probably best for the woman’s health if she replaces the nutrients lost as a result of the OCs. Some patients already may not have good diets and/or absorption, so it is better to recommend that the patient replace the lost nutrients vs. not replacing them.”

Other Lifestyle Choices & Key Information

• Diet:• ~80% of having a better quality of diet is due to lifestyle change, while supplements

provide the extra 20% (common knowledge)• Suggest Mediterranean Diet • Why Isn’t Diet Enough? Blood is cycled because of the heart, but the lymphatic

system does not get filtered unless exercise • Sleep: The body has to sleep to repair itself• Blood Vessels: The blood vessels are the route that nutrients get to the cells; exercise,

quality sleep, and a quality diet are key to maintaining the health of blood vessels• Mitochondria: Humans receive all of their mitochondrial DNA from their mother, and

once mitochondrial DNA is damaged it cannot be repaired• Micronutrients: Micronutrients are needed to help the cells break down the

macronutrients so that food (carbohydrates, protein, and fats) can be used in the correct way

“What Supplements Do You Recommend For My

Children/Infant?”• Find out patient’s concerns about their children and why they are

considering the supplement for their child• Check label; ask Josh & other pharmacists if appropriate• Depending on the supplement, it may be better for the child to start

the supplement earlier in life than later in lifeProbiotics CoQ10 Magnesium & Calcium Vitamin B12

Depends on the Age, but some probiotics can be given from

birth

Has Not Been Significantly Studied in Children, but Dosings

Available for <18

Mg: 0-6 months: 30 mg/day, 7-12 months: 75

mg/day, 1-3 years: 80 mg/day ;Ca: 0-6 months:

200 mg/day; 7-12 months: 260 mg/day; 1-3

years: 700 mg/day

0-6 months: 0.4 mcg/day, 7-12

months: 0.5 mcg/day, 1-3 years:

0.9 mcg/day S

Future Directions• Create Repletion Protocol for Lacto-Ovo Vegetarians, Vegans,

Fruitarians, & Patients Who Eat Raw/Living Food• Create Repletion Protocol for Elderly on Certain Medications• Create Repletion Protocol for Pregnant Women on Certain

Medications• Monitor Results of the Different Treatments for the Drug Nutrient

Depletions & Later Advertise Those Results if Wanted

Conclusions Regarding Customer Service

• Want to improve the patient’s quality of life while also making $ (ultimate goal is for the patient to make a lifestyle change, not just to have improved quality of life)• Ideally, want good relationship with patient/customer and providers that

commonly prescribe medicines to Dilworth Drug, so that providers will recommend supplements to certain patients, improving health outcomes for the patients, which may improve health outcomes for pharmacies and providers• Can suggest in some cases for patients to start with cheaper (but quality)

supplements, and then increase to take more expensive supplements (let patient see the difference that taking one inexpensive supplement makes)• Can also suggest starting with one expensive supplement that may help improve

the patient’s overall health more significantly

Basic Takeaways• There are minimal studies on supplements, because drug companies will

not spend money to conduct clinical trials, because supplements cannot usually be patented• Discussed pathophysiology of drug nutrient depletions and mechanisms

of drug nutrient repletion• There are a lot of drugs that are taken together that may deplete the

same nutrients• Many of the nutrients have functions that overlap• Discussed cost of the medicines• Discussed what to say to customers & providers

Studies Used For Each Nutrient Depletion Regiment References

• Probiotics: • Issa I, Moucari R. Probiotics for Antibiotic Associated Diarrhea: Do We Have a Verdict?. World J Gastroenterol [Internet]. 2014 Dec 21

[cited 2016 October 16]; 20(47): 17788-17795. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273129

• CoQ10: • Banach M, Serban C, Ursoniu S, Rysz J, Muntner P, Toth PP, Jones SR, Rizzo M, Glasser SP, Watts GF, Blumenthal RS, Lip GY, Mikhalilidis DP,

Sahebkar A. Statins therapy and plasma coenzyme Q10 concentrations- A systematic review and meta-analysis of placebo-controlled trials. Mayo Clinic Proc. [Internet]. 2015 January [cited 2016 OCTOBER 16]; 90(1): 24-34. Available from: www.mayoclinicproceedings.org/article/S0025-6196(14)00799-X/abstract

• Landbo C, Almdal TP. [Interaction Between Warfarin and Conenzyme Q10]. Ugeskr Laegar [Internet]. 1998 May 25 [cited 2016 October 16]; 160(22): 3226-7. Available from: https://www.ncbi.nlm.nih/gov/pubmed/9621803

• Engelsen J, Nielsen JD, Hansen KF. [Effect of Conenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment. A randomized, double-blind, placebo-controlled cross-over trial]. Ugeskr Laegar [Internet]. 2003 Apr 28; 165 (18):1868-71. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12772396

• Vitamin B12:• Pfilpsen MC, Oh RC, Saquil A, Seehusen DA, Seaquist D, Topolski R. The prevalence of Vitamin B(12) Deficiency in Patients With Type 2

Diabetes: A Cross Sectional Study. J Am Board Fam Med [Internet]. 2009 Sep; 22(5): 528-34. Available from: www.jabfm.org/content/22/5/528.long

• Isaac TG, Soundarya S, Christopher S, Chandra SR. Vitamin B12 Deficiency: An Important Reversible Co-Morbidity in Neuropsychiatric Manifestatios, Indian J Pshcol Med [Internet]. 2015 [cited 2016 October 16]; 37(1). Available from: httpsL://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341306

Studies Used For Each Nutrient Depletion Regiment References

• Magnesium: • Park CH, Kim EH, Roh YH, Kim HY, Lee SK. The Association Between the Use of Proton

Pump Inhibitors and the Risk of Hypomagnesemia: A systematic Review and Meta-Analysis. PLoS One [Internet]. 2014 November 13 [cited 2016 October 16]; 9(11): e1122558. Available from: http://www/ncbi.nlm.nih.gov/pubmed/25394217

• Oral Contraceptives:• Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral Contraceptives and changes

in nutritional requirements. Eur Rev Pharmacol Sci [Internet]. 2013 July [cited 2016 October 16]; 17(13): 1804-13. Available from: www.europeanreview.org/article/4579

• Widely used Reference:• Lexicomp [Internet]. Hudson, Ohio: Wolters Kluwer. 2016. Lexi-Drugs; [cited 2016

October 4]. Available from: https://online.lexi.com/lco/action/home

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Final Most Common Drug Nutrient Depletions (1)

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