Viagra for Alzheimer’s Disease?

Is Viagra the New Miracle Drug?
Or is Big Science Misleading Us Again?

 

by Jerry Bergman, PhD

Those of us involved in researching the evidence for and against evolution have often witnessed claims made which turn out to be over-hyped, or even false. Thus for good reason they eventually are overturned. The list is long and is covered in many of the reviews posted on this website. Drug claims are also not immune from this problem. Both over-hyped evolution assertions and exaggerated drug claims suffer from the same problem.

Colored Glasses

The problem is that the supporters of certain drugs and evolution are often true believers. Whether for evolution or miracle drug claims, their biased glasses distort their reality. This influences them to see what they want to see. Another problem is so-called “Big Science,” defined as the powerful academic institutions, journal editors, and lobbyists who claim to “speak for science” to the public. While pretending to value “science,” they actually repudiate it by censoring skepticism about what they tout as the “scientific consensus” about evolution and about the effectiveness of certain drugs they support.[1]

Scientists can be motivated to wear biased glasses in the lab for many reasons. These include the quest for fame, the need to renew research grant funding, the desire to be awarded tenure, or the desire for self-satisfaction. Most research depends on outside grants, which require evidence of future research breakthroughs in order to be renewed.

Wearing my skeptic’s glasses, I was asked to look into the claim made by promising new research from the Cleveland Clinic.  The research claimed that Viagra can reduce the onset of the symptoms of Alzheimer’s disease and even prevent persons from developing the disease by as much as a whopping 69 percent![2] This is no small claim.

About Alzheimer’s Disease

Alzheimer’s is an irreversible disease that destroys memory along with the ability to reason and carry out normal daily living activities. The symptoms of the disease become progressively worse over time, and its victims eventually require full-time care.[3] I know its effect first hand from my own mother’s experience. She was struck with the disease in her early 60s and lived to be 75. She required full-time care for most of this time.

The Alzheimer’s Association estimates that over 6.5 million Americans have Alzheimer’s disease.[4] It is the most common cause of dementia in the United States today. Alzheimer’s is also the sixth-leading cause of death in the United States.[5] The vast majority of those who develop Alzheimer’s dementia are older than age 65. An estimated 13.1 percent of people age 75 to 84 and 33.2 percent of people age 85 or older, come down with Alzheimer’s dementia.[6] Alzheimer’s, like other common chronic diseases, develops as a result of many factors.

Prevention

The main steps to reduce Alzheimer’s risk are similar to those that reduce the risk of the other leading killers. These include adopting healthy lifestyle, including regular exercising (walking, yoga, lifting weights, and swimming), consuming a healthy diet, and participating in frequent social activity (involvement with friends, neighbors, and church groups), as well as maintaining heart health and monitoring known cardiovascular risk factors (especially high blood pressure, diabetes, and obesity).[7]

Added to these recommendations, according to the Cleveland Clinic Research, may be taking Viagra (the research used sildenafil, the generic brand of Viagra) daily. The early sildenafil studies indicate that those on this therapy are 69 percent less likely to develop the disease.[8] The research, published in one of the leading science magazines,[9] concluded that using

retrospective case–control pharmacoepidemiologic analyses of insurance claims data for 7.23 million individuals, we found that sildenafil usage was significantly associated with a 69% reduced risk of Alzheimer’s disease (hazard ratio 0.31, 95% confidence interval 0.25–0.39, P < 1.0 × 10^–8). Propensity score-stratified analyses confirmed that sildenafil is significantly associated with a decreased risk of Alzheimer’s disease across all four drug cohorts tested (diltiazem, glimepiride, losartan and metformin) after adjusting for age, sex, race and disease comorbidities. ….  sildenafil increases neurite growth and decreases phospho-tau expression in neuron models ….  supporting mechanistically its potential beneficial effect in Alzheimer’s disease. The association between sildenafil use and decreased incidence of Alzheimer’s disease does not establish causality, which will require a randomized controlled trial.[10]

All drugs have side effects. When altering the body’s physiology with drugs, unintended consequences, some minor, some major, always result, producing a risk-benefit ratio. The concern is, do the benefits outweigh the risks? This question must be asked for, not only the entire trial population, but also for each individual person who decides to take a drug.

Potential Harmful Effects

The other side of the debate includes the harmful effects of taking the drug. In the case of medication for erectile dysfunction, in an evaluation of the side effects from 1998 (the year Viagra was approved) through 2007, Viagra was implicated in 1,824 deaths, mostly heart attacks. Cialis (approved in 2003) was linked to 236 deaths, and Levitra (also approved in 2003) was linked to 121 deaths. These three medications caused, or significantly contributed, to 2,500 nonfatal heart attacks and other potentially serious heart problems. Furthermore, more than 25,000 other potentially serious side effects were recorded; among them include mini-strokes, as well as some vision and hearing loss.[11] This is a large number of cases, but the cases of serious side effects were estimated to be less than two percent of all of the millions of persons taking the drug during the nine years the data was collected.[12]

It is difficult to know for certain that these medications caused the problems listed above. Men taking these drugs are likely to be older and many had health problems which originally caused their erectile dysfunction. Thus, the population using the drug had a much higher risk for heart attacks and mini-strokes than the general public. The ideal research method would be to give half of the research population a placebo. However, the problem with this methodology is that, if the claimed erectile medicine does not work after a few tries, the subjects will likely stop taking it. This would negate the entire goal of the research.

How Does Viagra Work?

Viagra (citrate salt of sildenafil) is a vasodilator, which causes the body’s arteries to relax, producing a larger internal diameter. It thus allows increased, less-impeded, blood flow, lowering blood pressure and also allowing increased blood flow to the penis, facilitating an erection. Viagra was originally developed to lower blood pressure. The patients taking this medicine noted that it not only lowered blood pressure, but also improved their sex life. It thus was eventually more often prescribed off-label, meaning that it was not designed to treat erectile dysfunction, but could be prescribed to treat erectile dysfunction at the doctor’s discretion. In addition, it may actually lower blood pressure and consequently reduce one of the common causes of death. One possibility is that the 1,824 deaths, mostly from heart attacks, could have been higher if these patients were not taking the drug.

The scientific reason Viagra works is that it is an inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5. This alpha-adrenergic blocking agent lowers blood pressure by preventing the norepinephrine hormone from tightening the muscles in the walls of the smaller arteries and veins.

Many Drugs Tried and Failed

Other drugs have been tried and have failed to reduce the symptoms of Alzheimer’s disease. Although sildenafil use to treat Alzheimer’s disease looks very promising, it may turn out to be a disappointment. On the other hand, one advantage with sildenafil is that an enormous amount of clinical experience already exists on the drug. Scientists have good data on the potential problems, thus can monitor for signs of heart disease and determine the specific type of patients that are at higher risk.

Thus, the current off-label use of sildenafil could influence fast tracking of its use.[13]  The possibility of a cure, or delay of disease progression, appears to be better than doing nothing. Doing nothing is where we are at now, once the disease has been confirmed by use of the current imperfect testing. Because many causes of dementia exist, at present only a post-mortem biopsy can determine for certain whether the person had Alzheimer’s disease.

Alzheimer’s Cause Still Unknown

One attempted cure, or approach to delay the onset of the disease, is the use of a drug that reduces the production of amyloid plaques. For years, it was noted that amyloid plaques and neurofibrillary tangles were commonly found in Alzheimer’s patients.[14] Thus, it was logical to conclude that reducing these abnormalities would reduce the severity, and possibly even the occurrence, of the disease. It has not.

If amyloid plaques drive Alzheimer’s disease, why have anti-amyloid therapies failed to slow cognitive decline? Reasons include the fact that amyloid plaques and neurofibrillary tangles are only two results of the pathology caused by Alzheimer’s disease. Other conditions which cause amyloid plaques and neurofibrillary tangles may be at the root of the problem.

Here’s an analogy that illustrates the difficulty of assigning causation: suppose an examination of a flat tire reveals two leaks. After those are fixed, suppose the tire still goes flat. Then, another source of the leak is found: a defective rim caused the two leaks. A new tire rim was required to solve the problem. Many diseases, similarly, might have a variety of causes, as well as producing a variety of symptoms. Alzheimer’s disease may require treatment for a specific set of symptoms, or require a cocktail of treatments.[15]

Summary

If nothing else, Alzheimer’s disease research is proving one reality, namely that the human brain is far more complex than believed even a few years ago. Further research to treat Alzheimer’s disease will no doubt open up to the discovery to a new level of brain complexity. This fact supports the reality that the human body is fearfully and wonderfully made.[16]

Update 10/05/2022: The National Institutes of Health (NIH) recently concluded that Viagra and Cialis do not reduce the risk of Alzheimer’s and related dementias. The research reported on in my paper found that Viagra can reduce the onset of the symptoms of Alzheimer’s disease, and even prevent persons from developing the disease by as much as a whopping 69 percent. The new study evaluated the hypothesis that phosphodiesterase-5 inhibitors was associated with a reduced incidence of Alzheimer’s disease and related dementia. The researchers used a patient-level cohort study of Medicare claims and also cell culture-based phenotypic assays to determine if the drug reduced molecular abnormalities relevant to Alzheimer’s disease in cell culture-based phenotypic assays.

In brief, their results did not provide support to the hypothesis that phosphodiesterase-5 inhibitors are promising candidates for deducing the rate of Alzheimer’s disease and related dementia. One problem was the protocol of the new research was very different from the research I reported. The goal for medical research is to determine if a causal relationship exists between the use of a drug and the reduction of a disease requires several studies.

As far as I know, only two exist which is inadequate to make firm conclusions. What needs to be looked at now is the research protocol difference between the two studies and the patient population of each. Comparing the two studies can help understand why a difference existed. Was it the subject population traits? The criteria used to diagnose Alzheimer’s disease? The specific drug and dosage used?  Conflicting results are not at all unusual in drug research and require more research. In this case more research is recommended. 

References

[1] Coppedge, David F., Should Big Science Blame the Public for Mistrust?, Creation/Evolution Headlines, 19 August 2022.

[2] Cleveland Clinic, Cleveland Clinic Research Identifies Sildenafil as Candidate Drug for
Alzheimer’s Disease (original press release from December 2021). Cleveland Clinic: Newsroom, 6 December 2021.

[3] Texas Health and Human Services, What is Alzheimer’s Disease? Questions and Answers. Texas Department of State Health Services, 2022.

[4] Alzheimer’s Disease Facts and Figures, 2022.

[5] Xu, J.Q., S.L. Murphy, K.D. Kochanek,  and E. Arias,  Mortality in the United States, 2018, NCHS Data Brief, No. 355. Hyattsville, MD: National Center for Health Statistics, 2020.

[6] Hebert, L.E., J. Weuve, P.A. Scherr, and D.A. Evans, Alzheimer disease in the United States (2010-2050) estimated using the 2010 Census. Neurology 80(19): 1778-1783, 7 May 2013.

[7] Norton, S., F.E. Matthews, D.E. Barnes, K. Yaffe, and C. Brayne, Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. The Lancet Neurology 13(8): 788-794, doi:10.1016/S1474-4422(14)70136-X, 2014.

[8] Cleveland Clinic, ref. 2, 2021. e

[9] Fang, J., P. Zhang, and Y. Zhou et al., Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer’s disease. Nature Aging 1!12): 1175–1188, 2021.

[10] Fang et al., ref. 9, 2021.

[11] Castleman, Michael, Warning to Men: Erection Drugs Just Might Kill You, Psychology Today Magazine, 5 December 2014.

[12] Viagra, RxList, https://www.rxlist.com/viagra-drug.htm#indications, 2022.

[13] Kozlov, Max, 2Will the FDA change how it vets drugs following the Alzheimer’s debacle?
Nature,  May 2022.

[14] Haass, Christian, and Dennis Selkoe, If amyloid drives Alzheimer disease, why have anti-amyloid therapies not yet slowed cognitive decline? PLoS One, 21 July 2022.

[15] Baker, Toni, Peptide delivered by nasal spray can reduce seizure activity, protect neurons in Alzheimer’s, epilepsy (Augusta University, 16 Aug 2022).

[16] Wile, Jay, and Marilyn Shannon, The Human Body: Fearfully And Wonderfully Made. Indianapolis, IN: Apologia Educational Ministries Inc., 2001.

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Dr. Jerry Bergman has taught biology, genetics, chemistry, biochemistry, anthropology, geology, and microbiology for over 40 years at several colleges and universities including Bowling Green State University, Medical College of Ohio where he was a research associate in experimental pathology, and The University of Toledo. He is a graduate of the Medical College of Ohio, Wayne State University in Detroit, the University of Toledo, and Bowling Green State University. He has over 1,300 publications in 12 languages and 40 books and monographs. His books and textbooks that include chapters that he authored are in over 1,500 college libraries in 27 countries. So far over 80,000 copies of the 40 books and monographs that he has authored or co-authored are in print. For more articles by Dr Bergman, see his Author Profile.