A Lyme Disease Antibiotic Guide

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Updated: 6/17/24

Herbal & Prescription Lyme Disease Antibiotics

In this chapter, you will learn how to build a Lyme disease herbal or prescription antibiotic treatment. Later in this guide, I provide 10 sample herbal and prescription antibiotic treatment plans, including the dosing regimens I find effective.

The focus of this article is on Lyme germ treatment. For information about treating Lyme disease coinfections, see:

Before I describe the plan, be aware that chronic Lyme disease recovery requires more than antibiotics. I cannot emphasize this point strongly enough. Treating Borrelia, the Lyme germ, with antibiotics is complicated because limited research shows which treatment regimens work best. As a result, many Lyme-literate medical doctors (LLMDs), like myself, prescribe antibiotics based on theory and our collective observation. Theory and observation show us that combinations of antimicrobials work better than single agents alone. It is critical that a Lyme disease treatment regimen addresses the first 10 steps outlined in my Lyme disease treatment guidelines, The Ross Lyme Support Protocol. These steps are designed to revive health and to boost the immune system. Even a year or more into treatment, when a person is feeling better, these steps are essential to speed recovery by supporting the immune system.

Therefore, the plan that follows is not—and cannot be—a complete or comprehensive guide. Rather, it reflects how I organize the available knowledge and understanding about Lyme disease to subsequently create effective Lyme disease antibiotic treatments.

Lyme Terminology 101

Before I describe herbal and prescription antibiotic approaches I find helpful treating Lyme in my Seattle practice, let’s talk about terms.

Lyme Has Two Extracellular Forms

Outside of cells, Lyme infection has two different looks, or forms. One form is the spirochete and the other is a microscopic cyst. Spirochetes can morph into cysts and cysts into spirochetes. Cysts are sometimes referred to as round bodies. An effective treatment approach must address both forms.

Lyme Has Two Growth States

Research first published in 2015 shows that Lyme has two different growth states. There is a growing phase of the germs and there is a persister phase. Think of the persisters as germs that are in hibernation. These persisters—hibernating phase germs—ignore regular standard antibiotics we traditionally used to treat Lyme.

Lyme Locations

Lyme can live outside of cells and inside of cells. Inside of cells, Lyme exists without a cell covering known as an L-form. Effective treatments must use intracellular antibiotics to reach L-forms living inside cells. Fortunately, intracellular antibiotics also reach Lyme outside of cells, too. As an example, penicillins (like amoxicillin) and cephalosporins (like cefuroxime) only work outside of cells. Macrolides (like clarithromycin) and tetracyclines (like doxycycline), work in the intracellular and extracellular spaces. Antibiotics that work on germs inside and outside of cells include the tetracyclines, macrolides, rifamycins, and azoles.

Furthermore, while herbal antibiotics may work inside of cells, it is not clear from research that they do. However, I have seen wonderful recoveries for many on herbal antibiotics, so I assume the ones I recommend in this article help with intracellular Lyme.

Putting Forms and Growth States Together

Lyme spirochetes and cysts can exist in growing phases and in persister phases. Some lab experiments suggest that the great majority exist in the growing phase; however, prolonged use of regular antibiotics may push a greater portion of the germs into the persister phase.

By “Antibiotics” I Mean

In this article, by antibiotics I mean prescription and herbal medicines that have antimicrobial effects against the Lyme germ. In my practice, I often mix herbal and prescription options together.

Lyme Disease Antibiotics Overview

The following are four general rules I use to develop a Lyme disease antibiotic regimen:

  • Rule 1: Combine antibiotics to treat all forms of the germ.
  • Rule 2: Combine antibiotics to treat Lyme living outside and inside of cells.
  • Rule 3: Combine antibiotics that work in different ways to attack the germ from different angles.
  • Rule 4: Treat all growth phases of Lyme at the same time. This means treatments should include antimicrobials that address persisters, in addition to the growth phase of the germ.

Herbal and Prescription Antimicrobials by Function

Be aware the doses I provide below are for adults. Use these same prescriptions with children but at lower doses. For pediatric dosing, talk with your family physician or pediatrician. Tetracyclines can be used in children under eight, but there is a risk of tooth staining. This staining seems not to be an issue if they are used for a month or less.

Antimicrobials that Kill Growing Phase Spirochetes

Extracellular

Penicillins

  • Amoxicillin 500 mg 1 to 2 pills 3 times a day. As an alternative to IV antibiotics take 3 to 4 pills 3 times a day.
  • Amoxicillin/Clavulanic Acid 875 mg/125 mg 1 pill 2 times a day.
  • Bicillin LA 2.4 million units IM (intramuscular injection) 3 times a week with one day between each injection.

Cephalosporins

  • Ceftriaxone 2 gm IV 2 times a day for 4 days in a row then off for 3 days every 7 days.
  • Cefotaxime 2 gm IV every 8 hours.
  • Cefuroxime 500 mg 1 pill 2 times a day.
  • Cefdinir 300 mg 1 pill 2 times a day.

Additional IV Antibiotics

Vancomycin, imipenem, and ertapenem (Ivanz) are possible alternatives if someone is allergic to ceftriaxone or cefotaxime.

Intracellular and Extracellular

Macrolides

  • Clarithromycin 500 mg 1 pill 2 times a day.
  • Azithromycin 500 mg 1 time a day or 500 mg IV 1 time a day.

Tetracyclines

  • Doxycycline 100 mg 1 or 2 pills 2 times a day or 200-400 mg IV 1 time a day.
  • Minocycline 100 mg 1 pill 2 times a day.

Antimicrobials that Kill Growing Phase Cysts

Note: I work with the following anti-cyst agents based on the mechanism by which these antibiotics work and some scientific experiments. For the rifamycins, no laboratory experiments show these agents work against cysts. Clinically, I see great benefit in using the rifamycins as my anti-cyst agents, so I list them here.

Rifamycins

  • Rifampin 300 mg 2 pills 1 time a day or 1 pill 2 times a day.
  • Rifabutin 150 mg 2 pills 1 time a day.

Azoles

  • Tinidazole 500 mg 1 pill 2 or 3 times a day usually pulsed 4 days on then 3 days off every 7 days.
  • Metronidazole 500 mg 1 pill 2 or 3 times a day usually pulsed for 4 days on then 3 days off every 7 days.

Herbal

  • Grapefruit seed extract 250 mg 1 pill 2 times a day. Note: this is an herbal antibiotic that I find as effective as the prescription options in this list.

Antimicrobial Herbs that Kill Growing Phase Spirochetes & Cysts and L-forms

Based on my observations, these herbal combination options have as good of a chance as the prescription options. They appear to kill intracellular and extracellular Lyme, too, based on the clinical benefit I see in my medical practice.

  • Cat’s Claw and Otoba Bark Tinctures 30 drops of each 2 times a day. Start at 5 drops 2 times a day and add 1 drop per dose per day until you reach 30 drops 2 times a day. If you get a Herxheimer reaction, stop increasing the dose until it has passed.
  • Cat’s Claw and Japanese Knotweed Tinctures 30 drops of Cat’s Claw 2 times a day and ½ tsp of Japanese Knotweed 3 times a day. Work up to these doses over 30 days. Start Cat’s Claw at 5 drops 2 times a day and add 1 drop per dose per day until you reach 30 drops 2 times a day. Start the Japanese Knotweed at ¼ tsp 3 times a day and in two weeks increase to ½ tsp 3 times a day.

Quinine Derivatives to Boost Intracellular Antibiotics

Intracellular

Inside of cells, Lyme may live in cave-like structures called vacuoles. In these vacuoles, Lyme germs create a hostile acidic environment that can limit the effectiveness of various antibiotics. Quinine derivatives, like hydroxychloroquine (Plaquenil), can make the inside of cells more basic (less acidic), which can help the tetracyclines and macrolides mentioned above work better.

  • Hydroxychloroquine (Plaquenil) 200 mg 1 pill 2 times a day.

Herbal and RX Antimicrobials that Treat Persisters

Treating persisters is a newer area in Lyme treatment. To help justify these various antimicrobial options, in this section I describe the experimental basis behind my recommendations. These options are ones I am using with various degrees of success in my Seattle practice. They all have either laboratory experiments or published human experiments supporting their use.

Laboratory-Based Experiment Options

The following prescription and herbal medicine options have been shown in lab experiments to kill persisters, which I am incorporating into my treatments of Lyme and/or Bartonella.

  • Disulfiram 4-5 mg/kg body weight 1 time a day. This is the final dose goal. It can take 3 to 4 months to reach this dose. For specific dosing information, including how to increase the dose, see Disulfiram (Chapter 23).

Disulfiram is shown in lab experiments by Jayakumar Rajadas, PhD and colleagues at Stanford to treat Lyme persisters. Ying Zhang, MD and colleagues at Johns Hopkins found disulfiram does not work against Bartonella, however. Furthermore, Dr. Rajadas and Dr. Zhang both showed that disulfiram can treat growing Lyme, although it is only moderately effective. Disulfiram is a drug used to treat alcoholism that is being repurposed to treat Lyme.

  • Methylene Blue 50 mg 2 times a day.

Dr. Zhang and colleagues at Johns Hopkins University have shown methylene blue treats growing and persister states of Lyme. Methylene blue is approved to treat a problem called methemoglobinemia where methylene blue causes hemoglobin to release oxygen. Methylene blue is repurposed to treat Lyme and Bartonella.

  • Liposomal Oregano, Cinnamon, and Clove Oils 1 capsule 2 times a day.

Dr. Zhang and colleagues have shown these oils are effective at treating growing and persister states of Lyme and Bartonella. Of the various herbal options listed here, this is my go-to favorite based on the clinical benefits I see in my practice.

  • Cryptolepis 5 ml 3 times a day.

This herbal medicine is traditionally used to treat Babesia and malaria. In two different studies in 2021, however, Dr. Zhang and colleagues have shown Cryptolepsis is effective at treating growing and persister forms of Bartonella and Lyme.

  • Japanese Knotweed ½ tsp 3 times a day. Start at ¼ tsp 1 time a day and then increase after two weeks to ½ tsp 3 times a day.

This herbal medicine is traditionally used to treat Lyme and Bartonella as described in the various books by master herbalist Stephen Buhner. Dr. Zhang and colleagues have also shown that Japanese knotweed treats growing and persister states of Lyme and Bartonella.

  • Cat’s Claw 30 drops 2 times a day.

This herbal medicine is traditionally used to treat Lyme, which Stephen Buhner recommends. Additionally, Dr. Zhang and colleagues have shown that it treats persister Lyme.

Human-Based Experiment Options

Here is a list of prescription medications shown in human experiments to help with persister Lyme.

  • Disulfiram 4 to 5 mg/kg body weight 1 time a day. This is the final dose goal. It can take 3 to 4 months to reach this dose. For specific dosing information, including how to increase the dose, see Disulfiram (Chapter 23).

Ken Liegner, MD  published a case report of more than 70 people he treated with disulfiram as a solo agent. Based on his reports and based on my experience, this repurposed drug is effective at putting about 36 percent of people with Lyme into remission and may help a larger group to have symptom improvements. However, disulfiram is a very difficult drug to use. For more information on this read Disulfiram.

Historically, dapsone is used to treat Leprosy. Richard Horowitz, MD has promoted the use of dapsone-based regimens to treat both Lyme and Bartonella persisters. He researched both a 100 mg dapsone protocol and a 200 mg dapsone protocol. Similar to disulfiram, dapsone-based treatment is a harsh regimen with nearly 40 percent of people dropping out of treatment due to side effects. Based on Horowitz’ experiments and my use of the medication with my patients, I find improvements of 20 percent or so in those that can tolerate the treatment. A small percentage of patients can get into remission with this treatment.

Disulfiram-Only Regimens

I recommend disulfiram-only regimens to people who have taken extensive numbers of antibiotics for a year or more of treatment and remain ill. In this type of situation, it is possible that the antibiotics have pushed most of the remaining germs out of a growing state into a persister state.

Dr. Liegner’s research shows that when disulfiram is used as a solo antibiotic, 36 percent of people can enter a period of extended remission. Therefore, in people who have failed years of antibiotics, without an active co-infection, I recommend a trial of disulfiram alone. Disulfiram does not have any benefit for Bartonella and is a very weak anti-Babesia agent. Because of this, I only use disulfiram alone to treat Lyme when these other germs are not active.

In the examples below, I also show that disulfiram can be used in combination with other antibiotics to treat perister Lyme where the other antibiotics treat growing phase Lyme.

What to Try If You Have Failed Years of Antibiotics

In my practice, I offer two persister-oriented regimens for those that have failed years of regular antibiotics. Both regimens have some published clinical evidence of benefit. One regimen I offer is a Horowitz dapsone-persister regimen. The other option I offer is a disulfiram-only regimen or a disulfiram-combination regimen. (See Lyme Disease Antibiotic Combination Examples below). You can read more details about how to take both regimens in:

Lyme Disease Antibiotic Combination Examples

In my experience, I find the prescription antibiotic combinations below work 85-90 percent of the time. The herbal combination options help 85-90 percent of the time. I find all these combinations more successful than the Andrographis combinations that some like herbalist Stephen Buhner and Bill Rawls, MD recommend. The Buhner/Rawls combination helps about 60-65 percent of the time in my clinical observations. To reach the success rates I describe here, it is essential to follow the first 10 steps of The Ross Lyme Support Protocol to support the immune system.

Key Points: Each combination

  • combines antibiotics to treat all forms of the germ;
  • combines antibiotics to treat Lyme living outside and inside of cells;
  • combines antibiotics that work in different ways to attack the germ from different angles; and
  • treats all growth phases of Lyme at the same time. Treatments include antimicrobials that address persisters, in addition to the growth phase.

1. Macrolide plus Azole plus Liposomal Essential Oils

  • Clarithromycin (Biaxin) 500 mg 1 pill 2 times a day.
  • Tinidazole 500 mg 1 pill 2 or 3 times a day.
  • Liposomal Cinnamon, Clove, and Oregano Oil 1 capsule 2 times a day.

Key Points:

  • Tinidazole treats cysts and can remove biofilms that block the immune system and antibiotics. (See Biofilms: Lyme Disease Gated Communities for more information about biofilms and treatments.)
  • Liposomal cinnamon, clove, and oregano oil can treat persister and growing forms of Lyme. Of the various herbal options to treat persisters, this is my go-to herbal anti-microbial based on benefits I see in my practice.

2. Macrolide plus Quinine Derivative plus Azole plus Methylene Blue

  • Azithromycin (Zithromax) 500 mg 1 pill 1 time a day.
  • Hydroxychloroquine (Plaquenil) 200 mg 1 pill 2 times a day.
  • Metronidazole (Flagyl) 500 mg 1 pill 2 or 3 times a day.
  • Methylene Blue 50 mg 2 times a day.

Key Points:

  • Since azithromycin is not as effective as other macrolides like clarithromycin, hydroxychloroquine is used to increase the effectiveness.
  • Tinidazole could be substituted for the metronidazole because it may remove biofilms more effectively.
  • Methylene Blue can treat persister Lyme. Be aware methylene blue costs nearly $350 a month. It also turns urine and stool blue and is very hard to scrub off porcelain toilets. Your clinician will need to order a glucose 6 phosphate dehydrogenase (G6PD) blood test. If this red blood cell antioxidant is low, then you should not take methylene blue. With low G6PD there is a risk that your red blood cells will break apart.

3. Macrolide plus Grapefruit Seed Extract plus Cryptolepis

  • Clarithromycin (Biaxin) 500 mg 1 pill 2 times a day.
  • Grapefruit Seed Extract 250 mg 1 pill 2 times a day.
  • Cryptolepis 5 ml 3 times a day.

Key Points:

  • Grapefruit seed extract is better tolerated than both tinidazole and metronidazole and supports killing of Lyme cysts.
  • Cryptolepis can treat persister and growing Lyme. If a person also has Babesia, cryptolepis can treat this, too.

4. Tetracycline plus Macrolide plus Grapefruit Seed Extract plus Japanese Knotweed

  • Doxycycline 100 mg 2 pills 2 times a day.
  • Clarithromycin (Biaxin) 500 mg 1 pill 2 times a day.
  • Grapefruit Seed Extract 250 mg 1 pill 2 times a day.
  • Japanese Knotweed ½ tsp 3 times a day.

Key Points:

  • Tetracyclines and macrolides both block protein production by binding to the protein production apparatus in germs called ribosomes. However, they each bind to a different part of the ribosome, thereby improving the blockade of protein production.
  • Japanese knotweed is added here to treat persister Lyme. It also may treat growing Lyme and can lower inflammation cytokines.

5. Penicillin plus Azole plus Liposomal Cinnamon, Clove, & Oregano Oils

  • Amoxicillin 500 mg 4 pills 3 times a day.
  • Tinidazole (Tindamax) 500 mg 1 pill 2 or 3 times a day for 4 days on and 3 days off in 7-day cycles.
  • Liposomal Cinnamon, Clove, and Oregano Oil capsules 1 pill 2 times a day.

Key Points:

  • 500 mg of amoxicillin is a very high dose, which is four times stronger than physicians prescribe for other infections, such as ear infections. I consider this dose nearly as effective as IV antibiotics. (See “IV Equivalent Treatments” below.)
  • This is a pulse-dose regimen of the tinidazole. It may be more effective than continuous regimens. (See “Pulse Dosing” below.)
  • The essential oils are added to treat persister Lyme.

6. Cephalosporin plus Tetracycline plus Rifampin plus Dapsone

  • Cefuroxime (Ceftin) 500 mg 2 pills 2 times a day.
  • Minocycline 100 mg 1 pill 2 times a day.
  • Rifampin 300 mg 2 pills 1 time a day.
  • Dapsone 100 mg 1 time a day.

Key Point:

  • This is a Horowitz-type persister protocol. The dapsone is included here to treat persisters.

7. Herbal Combination 1

  • Otoba Bark Extract plus Cat’s Claw 30 drops of each 2 times a day. Start at 5 drops of each 2 times a day and increase every day by 1 drop per dose until taking 30 drops of each 2 times a day. If increasing the dosages makes a person feel worse, they should not increase until the worsening improves. Take without food is best (i.e., do not take beginning 30 minutes before food through 2 hours after food, but you may take it with medicines and supplements).
  • Cryptolepis 5 ml 3 times a day.

Key Points:

  • I find this combination as effective as oral prescription antibiotic combinations. It works successfully as a support in a Lyme treatment about 85-90 percent of the time.
  • In addition to treating all forms of the germ, this combination supports the removal of biofilms.
  • The cryptolepis and the Cat’s Claw can treat persister and growing Lyme.

8. Herbal Combination 2

  • Cat’s Claw and Japanese Knotweed 30 drops of Cat’s Claw 2 times a day and ½ tsp of Japanese knotweed 3 times a day. Work up to these doses over 30 days. Start Cat’s Claw at 5 drops 2 times a day and add 1 drop per dose per day until you reach 30 drops 2 times a day. Start the Japanese knotweed at ¼ tsp 3 times a day and in two weeks increase to ½ tsp 3 times a day.
  • Liposomal Cinnamon, Clove, and Oregano Oil 1 pill 2 times a day.

Key Point:

  • Each of these herbal medicine options is shown in lab experiments to treat growing and persister phases of Lyme.

9. Tetracycline plus Rifamycin plus Disulfiram

  • Minocycline 100 mg 1 pill 2 times a day.
  • Rifampin 300 mg 2 pills 1 time a day.
  • Disulfiram 4-5 mg/kg body weight. Work up to this dose slowly over 2-4 months, then remain on the disulfiram at the peak dose for 4 months before tapering off.

Key Points:

  • Minocycine and rifampin in this combination are also useful for treating a Bartonella co-infection. Co-infections are other germs passed on during a tick bite. If someone has a co-infection, when possible, I choose antibiotic combinations that simultaneously treat Lyme germs and the co-infection germs.
  • The disulfiram is added here to treat persister Lyme. Note: disulfiram does not appear to treat Bartonella.

10. IV Antibiotic Regimen: Cephalosporin plus Azole plus Liposomal Cinnamon Clove and Oregano

  • Ceftriaxone (Rocephin) 2 gm IV 2 times a day for 4 days on and 3 days off.
  • Tinidazole 500 mg taken orally 1 pill 2-3 times a day for 4 days on and 3 days off in 7-day cycles.
  • Liposomal Cinnamon, Clove, and Oregano Oil 1 pill 2 times a day

Key Points:

  • Various antibiotics can be used as IV. I use this one most commonly because it is the easiest to administer and one of the lowest cost IV regimens. The ceftriaxone is given in a syringe and injected over 10 minutes. This is also a pulse-dose regimen (see below under “Special Considerations”). As an alternative, ceftriaxone could be given daily as 2 gm IV 1 time a day.
  • I have found various pulse-dose regimens of tinidazole to work. These include 2 weeks on and 2 weeks off, or in the regimen seen here.

Additional Herbal Antibiotic Only Regimens

For the latest on herbal antibiotic regimens that can treat more than one of the three Bs (Borrelia, Bartonella, and Babesia) at a time see Best Herbal Antibiotic Plans for Lyme, Bartonella, and Babesia.

Special Considerations for Lyme Disease Antibiotics

Antibiotics Alone Are Unlikely to Get You Well

This is the second time I am making this point because it is very important. It is essential to your recovery that, at a minimum, your treatment addresses the steps outlined in my Lyme disease treatment guidelines, The Ross Lyme Support Protocol (Chapter 4). Even a year or more into your treatment, these 10 steps are essential to resuscitate and support the immune system.

Pulse Dosing

Pulsing herbal antibiotics does not work well; therefore, I do not recommend it here. Clinically, continuous use of herbal antibiotics works best in most situations. The only time I pulse is for two months on and two months off when using regimens to address persister Lyme. For more information about this, see How to Treat Persister Lyme & Bartonella. Pay attention to the Burrascano-type regimen I mention.

Some prescription antibiotics can be given using pulse dosing. The idea is to start and stop the antibiotics. This allows the body to recover from the toxicity of some of the drugs while effectively killing the germ using high doses. Again, pulsing may also help with persister cells. As Lyme is a slow-growing germ, the spirochete form only requires two to three days for some antibiotics to work and then several days to recover and Lyme to start growing again. All the antibiotics mentioned in this article may be pulse-dosed except for azithromycin. One way to pulse is in a 4-day-on-and-3-day-off cycle. Many physicians have different ways of pulsing antibiotics.

IV Versus Oral Antibiotics

In my experience, I find most oral antibiotic combinations to work about 85 percent of the time, while IV equivalent treatments work about 90 percent of the time. Thus, the majority of people with chronic Lyme do not require IV antibiotics.

IV Equivalent Treatments

I find either benzathine penicillin G (Bicillin LA) 1.2 million units given 3-4 times a week or high dose oral amoxicillin 500 mg 3-4 pills given 3 times a day is nearly as effective as IV antibiotic regimens. These treatment regimens deliver effective drug levels that penetrate tissues and the brain.

Treatment Length

Continue treatment with antibiotics until you are well. For some, this may mean they achieve complete recovery; for others, it may not. At the beginning of treatment for someone with chronic Lyme, it is difficult to predict what the length and degree of recovery will be. For more information about this, see When Will I Start to Feel Better? (Lyme, Babesia, & Bartonella Timelines).

Generally, I suggest rotating a prescription antibiotic every six months to prevent resistance to that antibiotic. However, I find herbal antibiotics work well for a year or more without changing the herbs. Lyme does not easily develop herbal antibiotic resistance.

It is time to stop a full treatment when someone is either symptom-free for two months or the improvements have plateaued for four months after adjusting the regimen. On average, it can take two years to recover for someone with chronic Lyme. This is an average. Some are on the six-month program, while others may require years.

Follow the steps in Can’t Get Better? Do This to see what else to address if antibiotics are not working, or if you are at a plateau.

Remission

For some with chronic Lyme disease, a cure does not occur. Refer to Finished? And How to Prevent Relapse for a discussion of this.

Herxheimer Die-off Reaction

About 90 percent of the time when antibiotics are started or changed during a treatment, a person will initially worsen. This is often due to a Herxheimer die-off reaction. Refer to Herxheimer Die-off Reaction: Inflammation Run Amok for a discussion of this and practical steps you can take to prevent or treat it.

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About The Author

Marty Ross, MD is a passionate Lyme disease educator and clinical expert. He helps Lyme sufferers and their physicians see what really works based on his review of the science and extensive real-world experience. Dr. Ross is licensed to practice medicine in Washington State (License: MD00033296) where he has treated thousands of Lyme disease patients in his Seattle practice.

Marty Ross, MD is a graduate of Indiana University School of Medicine and Georgetown University Family Medicine Residency. He is a member of the International Lyme and Associated Disease Society (ILADS), The Institute for Functional Medicine, and The American Academy of Anti-Aging Medicine (A4M).

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