Two common classes of drugs linked to dementia

Recent reports have linked two common classes of drugs to dementia. Fortunately, there are alternatives to both.

If you’re worried about developing dementia, you’ve probably memorized the list of things you should do to minimize your risk—eating a healthy diet, exercising regularly, getting adequate sleep, and keeping your mind and soul engaged. In the past year, we’ve learned that some of the drugs you may be taking to help you accomplish those things could increase your risk of dementia. In two separate large population studies, both benzodiazepines (a category that includes medications for anxiety and sleeping pills) and anticholinergics (a group that encompasses medications for allergies and colds, depression, high blood pressure, and incontinence) were associated with an increased risk of dementia in people who used them for longer than a few months. In both cases, the effect increased with the dose of the drug and the duration of use.

Image: Thinkstock

These findings didn’t come entirely as a surprise to doctors who treat older people. “The Beer’s List published by the American Geriatrics Society has long recognized benzodiazepines, antihistamines, and tricyclic antidepressants as potentially inappropriate for older adults, given their side effects,” says Dr. Lauren J. Gleason, a physician in the Division of Aging at Harvard-affiliated Brigham and Women’s Hospital. Such drugs are on the list because they share troubling side effects—confusion, clouded thinking, and memory lapses—that can lead to falls, fractures, and auto accidents.

What the studies found

It’s important to note that neither of these studies was a randomized controlled clinical trial, so neither proved that either type of drug causes dementia.

The anticholinergic study. Researchers tracked nearly 3,500 men and women ages 65 or older who took part in Adult Changes in Thought (ACT), a long-term study conducted by the University of Washington and Group Health, a Seattle health care system. They used Group Health’s pharmacy records to determine all the drugs, both prescription and over-the-counter, that each participant took in the 10 years before starting the study. Participants’ health was tracked for an average of seven years. During that time, 800 of them developed dementia. When the researchers examined medication use, they found that people who used anticholinergic drugs were more likely to have developed dementia than those who didn’t use them. Moreover, dementia risk increased along with the cumulative dose. Taking an anticholinergic for the equivalent of three years or more was associated with a 54% higher dementia risk than taking the same dose for three months or less.

The University of Washington study is the first to include nonprescription drugs. It is also the first to eliminate the possibility that people were taking the drugs to alleviate early symptoms of undiagnosed dementia. For people who took anticholinergic bladder medications, the increased risk was just as high as for those taking tricyclic antidepressants, which are also anticholinergics.

The benzodiazepine study. A team of researchers from France and Canada linked benzodiazepine use to an increased risk of being diagnosed with Alzheimer’s disease. In the study, the greater people’s cumulative dose of benzodiazepines, the higher their risk.

The researchers relied on a database maintained by the Quebec health insurance program. From it, they identified nearly 2,000 men and women over age 66 who had been diagnosed with Alzheimer’s disease. They randomly selected more than 7,000 others without Alzheimer’s who were matched for age and sex to those with the disease. Once the groups were set, the researchers looked at the drug prescriptions during the five to six years preceding the Alzheimer’s diagnosis.

People who had taken a benzodiazepine for three consecutive months or less had about the same dementia risk as those who had never taken one. But those who had taken a benzodiazepine for three to six months had a 32% greater risk of developing Alzheimer’s, and those taking one for more than six months had an 84% greater risk than those who hadn’t taken one.

The type of drug taken also mattered. People who were on a long-acting benzodiazepine like diazepam (Valium) or flurazepam (Dalmane) were at greater risk than those on a short-acting one like triazolam (Halcion), lorazepam (Ativan), alprazolam (Xanax), or temazepam (Restoril).

Why these drugs have a stronger effect in older people

As we age, our ability to process medication changes. The kidneys and liver clear drugs more slowly, so drug levels in the blood remain higher for a longer time. People also gain fat and lose muscle mass over time. Both these changes affect the way drugs are distributed to and broken down in body tissues. And because these drugs are stored in body fat, they can continue to produce effects days after people stop taking them, especially in people with a higher proportion of body fat. In addition, older people tend to take more prescription and over-the-counter medications, each of which has the potential to suppress or enhance the effects of the others.

Why the drugs affect your mind

Both anticholinergics and benzodiazepines affect the activity of neurotransmitters—chemical messengers that work in the central nervous system—but the drugs work in slightly different ways.

Anticholinergic drugs block the action of acetylcholine. In the brain, acetylcholine is involved in learning and memory. In the rest of the body, it stimulates the autonomic nerves—those that regulate contractions of blood vessels, airways, and our cardiovascular and digestive systems. The strongest anticholinergic drugs include some antihistamines, tricyclic antidepressants, medications to control overactive bladder, and sleeping pills.

Benzodiazepines boost another neurotransmitter’s effectiveness. They make gamma-aminobutyric acid (GABA)—which slows the activity of neurons in the brain-—more potent. For that reason, they are used to calm anxiety and help people sleep.

If you take one of these drugs

Dr. Gleason suggests having a thorough discussion with your doctor to review the potential benefits and harms of these medications—and all the others you take. If a drug appears problematic, the two of you can explore alternatives by considering the reason it was prescribed and seeing if there is a different type of drug that can be used as a replacement.

Don’t stop taking the drugs on your own. It isn’t safe to quit most benzodiazepines and anticholinergic drugs “cold turkey.” Work with your clinician to develop a plan for tapering off them.

Medications to avoid or use briefly

Common drugs that might increase dementia risk Possible alternatives
Allergies, colds Anticholinergics

brompheniramine (Dimetapp)

carbinoxamine (Palgic)

chlorpheniramine (Chlor-Trimeton)

diphenhydramine (Benadryl)

hydroxyzine (Atarax, Vistaril)

cetirizine (Zyrtec)

desloratadine (Clarinex)

fexofenadine (Allegra)

loratadine (Claritin)

Anxiety Benzodiazepines

alprazolam (Xanax)

chlordiazepoxide (Librium)

clonazepam (Klonopin)

clorazepate (Tranxene)

diazepam (Valium)

flurazepam (Dalmane)

lorazepam (Ativan)

oxazepam (Serax)

bupropion (Wellbutrin)

buspirone (Buspar)

citalopram (Celexa)

fluoxetine (Prozac)

paroxetine (Paxil)

sertraline (Zoloft)

venlafaxine (Effexor)

Depression Anticholinergics

amitriptyline (Elavil)

clomipramine (Anafranil)

doxepin (Sinequan)

imipramine (Tofranil)

trimipramine (Surmontil)

bupropion (Wellbutrin)

buspirone (Buspar)

citalopram (Celexa)

fluoxetine (Prozac)

paroxetine (Paxil)

sertraline (Zoloft)

venlafaxine (Effexor)

Insomnia Anticholinergics

mirtazapine (Remeron)

nefazodone (Serzone)

trazodone (Desyrel)


estazolam (Prosom)

quazepam (Doral)

temazepam (Restoril)

triazolam (Halcion)


Nondrug approaches

practicing relaxation techniques

avoiding alcohol and heavy meals before bedtime

exercising vigorously early in the day

Urge incontinence Anticholinergics

darifenacin (Enablex)

fesoterodine (Toviaz)

flavoxate (Urispas)

oxybutynin (Ditropan)

solifenacin (Vesicare)

tolterodine (Detrol)

trimipramine (Surmontil)

trospium (Sanctura)

Nondrug approaches

bladder training

physical exercise

weight loss for overweight or obese women

Minimally invasive procedures

Botox injections

implantable bladder stimulators

Sources: DeGage SB, et al. “Benzodiazepine use and risk of Alzheimer’s disease: Case-control study,” BMJ (Sept. 9, 2014), Vol. 351, published online; Salahudeen MS et al. “Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: A systematic review,” BMC Geriatrics (March 15, 2015), Vol.15, No.31, published online.

Heartburn Drugs in Pregnancy Tied to Asthma in Babies


Taking heartburn medicines during pregnancy may increase the risk for asthma in the baby, a review of studies has found.

The analysis, in the Journal of Allergy and Clinical Immunology, combined data from eight studies that included more than 1.6 million patients. Follow-up ranged from five to 14 years.

Researchers found that H2 blockers, such as Pepcid or Tagamet, were associated with a 46 percent increased risk for childhood asthma. Taking proton pump inhibitors, such as Prilosec or Nexium, was linked to a 30 percent increase in risk. There was also some data suggesting an increased risk for skin allergies.

The reason for the connection is unclear, but animal studies suggest the drugs may interfere with digestion, leaving undigested food allergens that are then passed on to the fetus.

None of the studies accounted for all of the many factors that may influence asthma onset, and the authors acknowledge that no causal connection can be proven.

“Gastric reflux is common in pregnancy,” said the lead author, Dr. Aziz Sheikh, a professor of primary care at the University of Edinburgh, “and in the majority of women, it can be managed with lifestyle or diet changes.”

Where medicine is required, he said, “Milder treatments like chewable antacid tablets are the preferred option.”

  1. Taking Fish Oil During Pregnancy Is Found to Lower Child’s Asthma Risk

  2. Heartburn Drugs Tied to Dementia Risk

    Heartburn Drugs Tied to Kidney Problems

Stronger immune system with enhanced smell and taste in foods

Some prescription drugs dull your senses—and weaken your body’s ability to repair itself.

Recent Duke University research showed that enhancing the taste and smell of foods for patients in a retirement home resulted in stronger immune systems. (In a side benefit, they also got better grip strength in both hands!) In other studies, this same group of researchers found that flavor-enhanced foods in­creased the flow of saliva and, more importantly, salivary IgA (immunoglobulin A—the body’s natural antibiotic to fight pathogenic bacteria).

As Dr. David Williams, in his Alternatives newsletter, pointed out last year, these studies give us some extremely useful information when it comes to protecting ourselves from infections. Most of the infections we contract involve the mucus membranes—the moist outer layer of cells that covers the inner surfaces of the nose, mouth, lungs, and intestinal tract. “Good” bacteria that reside on these mucus membranes compete with the pathogens. The lymphatic system surrounding the mucus membranes produces natural antibodies like IgA. Higher levels of IgA equate to stronger immune status.

The area of the brain that processes smell and taste signals forms a direct neurological pathway to the immune system. In other words, pleasant tastes and smells strengthen your immune system. Delicious food is healing food, quite literally.

Unfortunately, many drugs can dull our smell and taste sense perception. “When you connect the dots,” Williams says, “it be­comes obvious that the astronomi­cal increase in the use of prescrip­tion and over-the-counter drugs, and changes in our food supply and dietary habits, are contributing to taste and smell perception prob­lems. And it’s not just a problem among our elderly. It’s occurring throughout all age groups. It’s a hidden risk factor for many of the health problems that have quietly slipped beneath the radar.”

Research also shows that certain food molecules exhibit hormone-like properties that stimulate or inhibit specific actions in the body. For example, the fish oils DHA and EPA bind to a hormone receptor which sets off a chain reac­tion that blocks inflammation and weight gain while improving blood sugar control. Last year, researchers discovered that obese individuals were more likely to have a defect in this receptor.

Other studies show that decreased taste and smell perception can decrease the desire for healthy foods, which reduces energy production. Similarly, loss of the sense of smell can signal other conditions such as Parkinson’s and Alzheimer’s.

Many medications not only disrupt the ability to taste and smell. They also reduce saliva production and increase cravings of salt and sugar. Less saliva makes us more vulnerable to infection. In addition, as we have reported, sugar causes type 2 diabetes and is now being linked to the development of Alzheimer’s, damages the heart, and reduces energy metabolism and synaptic activity in the brain—effectively making you dumber. In other words, our prescribed medications are not just risky because of the acknowledged side effects. They can make us sicker in a variety of less-understood ways.

Happily, there are natural ways to enhance your sense of taste and smell:

  • Reduce your use of medication;
  • Eliminate your exposure to cigarette smoke and airborne toxins;
  • Supplement with zinc, copper, magnesium, alpha lipoic acid, and vitamins A, B3, and B12 (studies suggest that large numbers of people are short of some of these nutrients, especially magnesium);
  • Get checked for hormonal or endocrine disorders, which can alter your taste and smell;
  • Try techniques such as “swishing” your liquids, deeply sniffing each item on your plate, and eating slowly and mindfully, to appreciate and help enhance flavor;
  • Practice nose breathing (don’t breathe through the mouth, especially when eating); and
  • Try some natural flavor enhancers, oils, and syrups like Flavorganics or Nature’s Flavors.

We would also suggest that increasing the diversity of our diet will create more diversity in our flavors and smells. What this research tells us is that our country’s increased reliance on processed foods and an industrialized food supply instead of on heritage breeds and heirloom species is destroying our health in new, surprising, and often subtle ways.

Have you lowered your cholesterol through lifestyle changes?

I chew my food more, added probiotics and some supplements (CQ10, folic+Vit B complex, Calcium+Magnesium+Zinc) and always avoided sugar (but still eats 3 bites of chocolates every other day. I breath more, watch my body for any signs of distress (skin issues, pains, lack of sleep, mouth health, sleep quality, urine color, others). I have lemons/citrus and herbs (essential oils – tea tree, eucalyptus, lemon grass for gums, skin and other uses).

I avoided pork and bacon and other processed foods and concentrated on whole foods, fish. I shop at farmer’s market, Trader’s joes and Whole Foods Store.

I spend 30min a day at NC.Fit in the bay area for my cross-fit training with a coach (group of 2 or 4 others). I garden during summer with my mom.

I try to have a good sleep, get sunshine, get a foot massage (body included) in the bay area and maintained a non-stressful work environment (although I work 2 jobs and still creating the next best thing in health concierge site with genetic tests, personalized diet, electronic appoint scheduling with docs and more at Coming Soon ).

I dance twice a month. I am happy in knowing that my effort in ensuring the health of my 80 yr old and finances of 5 college students (3 nieces in the Philippines and 2 children in the bay area) are not in vain and it keeps me going every day and face the world with energy and enthusiasm. And that I can share what I know about health in my blog


Resources for doctors and health consumers about genetic tests, clinical trials

Collecting buccal or cheek swab for genetic test

The following video will review proper techniques for collecting a buccal or cheek swab sample for processing in our laboratory in three easy steps. This will reduce the need for resample and is critical to yield good test results.

For general information about pharmacogenomics or drug-specific resources and clinical trials, visit the following websites:

Genetic tests description from Wiki

Clinical trials registries by country

The Value of DNA Sequencing

DNA sequencing: what it tells us about DNA changes in cancer, how looking across many tumors will help to identify meaningful changes and potential drug targets, and how genomics is changing the way we think about cancer.

The Link Between TCGA and Personalized Cancer Therapies

How cancers from the same anatomical site, such as breast cancer, are often genomically different. Knowing the genomic defect in an individual’s cancer can help doctors tailor treatment.

Cancer Genome ATLAS

Talking Glossary of Genetic Terms

FDA Guidance on Pharmacogenetic Tests and Genetic Tests for Heritable Markers

Click to access ucm071075.pdf

A comprehensive list of FDA-approved drugs that have pharmacogenetic information in their labeling. This list includes the drugs relevant to PGxOne™ reporting. is a registry and results database for clinical studies involving human participants. The database contains studies conducted around the world, funded by both public and private sources. This is a good source of information for clinical trials investigating the pharmacogenetic effects for drugs in development and as well as for drugs already commercially available.

FDA-approved drugs with biomarker/pharmacogenetics

A comprehensive list of FDA-approved drugs that have pharmacogenetic information in their labeling. This list includes the drugs relevant to PGxOne™ reporting.

National Institute of Health (NIH): Personalized Medicine is a registry and results database for clinical studies involving human participants. The database contains studies conducted around the world, funded by both public and private sources. This is a good source of information for clinical trials investigating the pharmacogenetic effects for drugs in development and as well as for drugs already commercially available.

National Institute of General Medical Sciences (NIGMS)

NIGMS is one of the NIH institute and part of the US Department of Health and Human Services. The NIGMS supports basic research and training nationwide, leading to advances in disease diagnosis, treatment and prevention. Along with other NIH institutes, the NIGMS contributes support to the NIH Pharmacogenomics Research Network (PGRN).

FDA Orange Book

The publication Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book).

A US Food and Drug Administration (FDA) database that provides timely consumer information on generic drugs

American Society of Genes and Cell Therapy

Clinical Trials by Therapeutic Area


Pharmacogenetics is the study of inherited genetic differences in drug metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects.[1] The term pharmacogenetics is often used interchangeably with the term pharmacogenomics which also investigates the role of acquired and inherited genetic differences in relation to drug response and drug behavior through a systematic examination of genes, gene products, and inter- and intra-individual variation in gene expression and function.[2]

In oncology, pharmacogenetics historically is the study of germline mutations (e.g., single-nucleotide polymorphisms affecting genes coding for liver enzymes responsible for drug deposition and pharmacokinetics), whereas pharmacogenomics refers to somatic mutations in tumoral DNA leading to alteration in drug response (e.g., KRAS mutations in patients treated with anti-Her1 biologics).[3]

Predicting drug-drug interactions

Much of current clinical interest is at the level of pharmacogenetics, involving variation in genes involved in drug metabolism with a particular emphasis on improving drug safety. The wider use of pharmacogenetic testing is viewed by many as an outstanding opportunity to improve prescribing safety and efficacy. Driving this trend are the 106,000 deaths and 2.2 Million serious events caused by adverse drug reactions in the US each year.[4][unreliable medical source?] As such ADRs are responsible for 5-7% of hospital admissions in the US and Europe, lead to the withdrawal of 4% of new medicines, and cost society an amount equal to the costs of drug treatment.[5]

Comparisons of the list of drugs most commonly implicated in adverse drug reactions with the list of metabolizing enzymes with known polymorphisms found that drugs commonly involved in adverse drug reactions were also those that were metabolized by enzymes with known polymorphisms (see Phillips, 2001).

Scientists and doctors are using this new technology for a variety of things, one being improving the efficacy of drugs. In psychology, we can predict quite accurately which anti-depressant a patient will best respond to by simply looking into their genetic code.[citation needed][dubious ] This is a huge step from the previous practice of adjusting and experimenting with different medications to get the best response. Antidepressants also have a large percentage of unresponsive patients and poor prediction rate of ADRs (adverse drug reactions). In depressed patients, 30% are not helped by antidepressants. In psychopharmacological therapy, a patient must be on a drug for 2 weeks before the effects can be fully examined and evaluated. For a patient in that 30%, this could mean months of trying medications to find an antidote to their pain. Any assistance in predicting a patient’s drug reaction to psychopharmacological therapy should be taken advantage of. Pharmacogenetics is a very useful and important tool in predicting which drugs will be effective in various patients.[6] The drug Plavix blocks platelet reception and is the second best selling prescription drug in the world, however, it is known to warrant different responses among patients.[7] GWAS studies have linked the gene CYP2C19 to those who cannot normally metabolize Plavix. Plavix is given to patients after receiving a stent in the coronary artery to prevent clotting.

Stent clots almost always result in heart attack or sudden death, fortunately it only occurs in 1 or 2% of the population. That 1 or 2% are those with the CYP2C19 SNP.[8] This finding has been applied in at least two hospitals, Scripps and Vanderbilt University, where patients who are candidates for heart stents are screened for the CYP2C19 variants.[9]

Another newfound use of pharmacogenetics involves the use of Vitamin E. The Technion Israel Institute of Technology observed that vitamin E can be used to in certain genotypes to lower the risk of cardiovascular disease in patients with diabetes, but in the same patients with another genotype, vitamin E can raise the risk of cardiovascular disease. A study was carried out, showing vitamin E is able to increase the function of HDL in those with the genotype haptoglobin 2-2 who suffer from diabetes. HDL is a lipoprotein that removes cholesterol from the blood and is associated with a reduced risk of atherosclerosis and heart disease. However, if you have the misfortune to possess the genotype haptoglobin 2-1, the study shows that this same treatment can drastically decrease your HDL function and cause cardiovascular disease.[10]

Pharmacogenetics is a rising concern in clinical oncology, because the therapeutic window of most anticancer drugs is narrow and patients with impaired ability to detoxify drugs will undergo life-threatening toxicities. In particular, genetic deregulations affecting genes coding for DPD, UGT1A1, TPMT, CDA and CYP2D6 are now considered as critical issues for patients treated with 5-FU/capecitabine, irinotecan, mercaptopurine/azathioprine, gemcitabine/capecitabine/AraC and tamoxifen, respectively. The decision to use pharmacogenetic techniques is influenced by the relative costs of genotyping technologies and the cost of providing a treatment to a patient with an incompatible genotype. When available, phenotype-based approaches proved their usefulness while being cost-effective.[11]

In the search for informative correlates of psychotropic drug response, pharmacogenetics has several advantages:[12]

  • The genotype of an individual is essentially invariable and remains unaffected by the treatment itself.[clarification needed]
  • Molecular biology techniques provide an accurate assessment of the genotype of an individual.[weasel words]
  • There has been a dramatic increase in the amount of genomic information that is available. This information provides the necessary data for comprehensive studies of individual genes and broad investigation of genome-wide variation.
  • The ease of accessibility to genotype information through peripheral blood or saliva sampling and advances in molecular techniques has increased the feasibility of DNA collection and genotyping in large-scale clinical trials.


The first observations of genetic variation in drug response date from the 1950s, involving the muscle relaxant suxamethonium chloride, and drugs metabolized by N-acetyltransferase. One in 3500 Caucasians has less efficient variant of the enzyme (butyrylcholinesterase) that metabolizes suxamethonium chloride.[13] As a consequence, the drug’s effect is prolonged, with slower recovery from surgical paralysis. Variation in the N-acetyltransferase gene divides people into “slow acetylators” and “fast acetylators”, with very different half-lives and blood concentrations of such important drugs as isoniazid (antituberculosis) and procainamide(antiarrhythmic). As part of the inborn system for clearing the body of xenobiotics, the cytochrome P450 oxidases (CYPs) are heavily involved in drug metabolism, and genetic variations in CYPs affect large populations. One member of the CYP superfamily, CYP2D6, now has over 75 known allelic variations, some of which lead to no activity, and some to enhanced activity. An estimated 29% of people in parts of East Africa may have multiple copies of the gene, and will therefore not be adequately treated with standard doses of drugs such as the painkiller codeine (which is activated by the enzyme). The first study using Genome-wide association studies (GWAS) linked age-related macular degeneration (AMD) with a SNP located on chromosome 1 that increased one’s risk of AMD. AMD is the most common cause of blindness, affecting more than seven million Americans. Until this study in 2005, we only knew about the inflammation of the retinal tissue causing AMD, not the genes responsible.[9]

Thiopurines and TPMT (thiopurine methyl transferase)

One of the earliest tests for a genetic variation resulting in a clinically important consequence was on the enzyme thiopurine methyltransferase (TPMT). TPMT metabolizes 6-mercaptopurine and azathioprine, two thiopurine drugs used in a range of indications, from childhood leukemia to autoimmune diseases. In people with a deficiency in TPMT activity, thiopurine metabolism must proceed by other pathways, one of which leads to the active thiopurine metabolite that is toxic to the bone marrow at high concentrations. Deficiency of TPMT affects a small proportion of people, though seriously. One in 300 people have two variant alleles and lack TPMT activity; these people need only 6-10% of the standard dose of the drug, and, if treated with the full dose, are at risk of severe bone marrow suppression. For them, genotype predicts clinical outcome, a prerequisite for an effective pharmacogenetic test. In 85-90% of affected people, this deficiency results from one of three common variant alleles.[14] Around 10% of people are heterozygous – they carry one variant allele – and produce a reduced quantity of functional enzyme. Overall, they are at greater risk of adverse effects, although as individuals their genotype is not necessarily predictive of their clinical outcome, which makes the interpretation of a clinical test difficult. Recent research suggests that patients who are heterozygous may have a better response to treatment, which raises whether people who have two wild-type alleles could tolerate a higher therapeutic dose.[15] The US Food and Drug Administration (FDA) have recently deliberated the inclusion of a recommendation for testing for TPMT deficiency to the prescribing information for 6-mercaptopurine and azathioprine. The information previously carried the warning that inherited deficiency of the enzyme could increase the risk of severe bone marrow suppression. It now carries the recommendation that people who develop bone marrow suppression while receiving 6-mercaptopurine or azathioprine be tested for TPMT deficiency.[citation needed]

Hepatitis C

A polymorphism near a human interferon gene is predictive of the effectiveness of an artificial interferon treatment for Hepatitis C. For genotype 1 hepatitis C treated with Pegylated interferon-alpha-2a or Pegylated interferon-alpha-2b (brand names Pegasys or PEG-Intron) combined with ribavirin, it has been shown that genetic polymorphisms near the human IL28B gene, encoding interferon lambda 3, are associated with significant differences in response to the treatment.[16] Genotype 1 hepatitis C patients carrying certain genetic variant alleles near the IL28B gene are more probable to achieve sustained virological response after the treatment than others, and demonstrated that the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus.