Podcast Summary
Peter Attia's Ad-Free Podcast Model and Zantac Controversy: Peter Attia values trust with his audience and runs an ad-free podcast, providing exclusive benefits for subscribers. He recently discussed the potential danger of Zantac and a citizen's petition to remove it from the market.
The host of The Peter Attia Drive, Peter Attia, has chosen not to run ads on his podcast and instead opted for a subscriber model to maintain trust and authenticity with his audience. He believes that access to valuable information is crucial for people to make better decisions and improve their lives. The podcast remains free, but members receive additional benefits such as exclusive show notes, Ask Me Anything episodes, and special deals on products he loves. Attia's decision was driven by his desire to maintain trust and only advocate for things he's passionate about. In a recent episode, Attia discussed the potential danger of the common drug Zantac (Ranitidine) and the citizen's petition filed by Valisher, an online pharmacy, to have it removed from the market due to its instability and potential carcinogenic properties.
Ensuring Safety and Authenticity of Medications: The Role of Valisure: Valisure's innovative approach validates every medication batch for contaminants before dispensing, reducing risks associated with contaminated drugs and promoting transparency and accountability in the pharmaceutical industry.
The discussion revolves around the importance of ensuring the safety and authenticity of medications, particularly generic drugs, following the discovery of contaminants in certain batches. The episode features an interview with David Light, who co-founded a pharmacy company, Valisure, that chemically validates every batch of medication before dispensing to customers. This additional step aims to reduce the risks associated with contaminated drugs, which have led several countries to withdraw certain medications from the market. The FDA has not yet requested a withdrawal of the drug in question, Zantech, but many other countries have done so. Listeners who take Zantech or know someone who does are encouraged to pass this information on. Valisure's approach addresses the need for increased transparency and accountability in the pharmaceutical industry.
Ensuring Medication Safety with Chemical Testing: Valisher Pharmaceuticals addresses the issue of self-reported drug manufacturing overseas by chemically testing medications at the end of the supply chain in the US, using a more economical and efficient spectroscopy-based approach.
The FDA's seal of approval on medications does not guarantee chemical testing, as the majority of drug manufacturing now takes place overseas and is self-reported to the FDA. This self-reporting system has potential for problems and cracks, and even before investigations into fraud, the system was deemed unacceptable for ensuring the quality and consistency of pharmaceuticals. Valisher Pharmaceuticals was founded in response to these issues, with the goal of chemically testing medications at the end of the supply chain in the US. However, the technology for this was expensive and cumbersome, so Valisher spent several years developing a spectroscopy-based approach to make the analysis more economical and efficient. Despite industry awareness of the problems, there was a lack of incentive for major players to address the issue, leading Valisher to attach their testing laboratory to an online pharmacy and launch just a year ago. While the idea of testing every single drug may have seemed insignificant and cumbersome in 2015, the growing concerns and advances in technology have made it a necessary solution to ensure the safety and efficacy of medications.
Valisher Pharmacy's Quality Control Differentiator: Valisher Pharmacy sets itself apart by purchasing large batches of medication for thorough analysis, ensuring better quality control and customer trust, despite potential cost increases.
Valisher Pharmacy differentiates itself from competitors by buying large batches of medication up to six months in advance for detailed analysis, which may increase costs but allows for better quality control and customer trust. This approach contrasts with competitors who focus on special packaging or other value-added services, and is particularly important for medications without clear biomarkers to indicate effectiveness. When Valisher's founder became suspicious of a patient's medication, he discovered that batches of certain generics could have significant differences in efficacy, leading him to investigate further and ultimately uncover systemic issues in the pharmaceutical industry. This discovery, made before Catherine's investigative work on drug fraud from India and China, underscores the importance of rigorous testing and quality control in the pharmacy industry.
Issue of inconsistent and low-quality generic medications: The founders of a company discovered the widespread problem of inconsistent and potentially dangerous generic medications, leading them to innovate technology to ensure medication validity before reaching patients, expanding their focus to include branded drugs as well.
There is a pervasive issue with the quality and consistency of generic medications, leading to potential health risks for patients. This problem is not limited to specific medication types or markets and has been anecdotally reported by various doctors. The founders of a company, originally intending to focus on validating generics, were surprised by the extent of the issue and the lack of transparency in the pharmaceutical supply chain. The founders, with a scientific background in molecular biology and experience in developing complex tools for analysis, aimed to innovate and develop technology to ensure the validity of medications before they reach patients. The issue of branded drugs also came to light as potentially susceptible to the same problems, and the company expanded its focus to include both generic and branded medications. The case of Valsartan recalls serves as a clear example of the risks and vulnerabilities in the global pharmaceutical supply chain.
Changes in manufacturing processes can lead to harmful impurities: Manufacturing changes can result in potent carcinogens, requiring thorough quality controls and testing to ensure drug safety
Changes in manufacturing processes for active pharmaceutical ingredients, like what happened with Val Sartan, can lead to the creation of harmful impurities, such as NDMA and DMF, which are potent carcinogens. These impurities can go undetected for years, leading to recalls and ongoing health concerns for patients. A solvent, like DMF, is necessary for making drugs and organic chemical reactions, but its use can result in unwanted side products and contaminants. The FDA recommends testing for known carcinogens like NDMA, but it's crucial to also consider other potential contaminants, like DMF, that could pose risks to patients. Companies must prioritize thorough quality controls and testing to ensure the safety and efficacy of their drugs.
Importance of thorough manufacturing processes and regular testing: Third-party testing companies like Valisher address limitations of FDA inspections and self-reporting in ensuring drug quality by analyzing every single batch of the supply chain.
The discovery of carcinogenic contaminants like NDMA in drugs like Volsartan and Losartan highlights the importance of thorough manufacturing processes and regular testing. The Good Manufacturing Practices (GMP) system is in place to ensure consistent and well-documented manufacturing, but it relies on self-reporting and FDA inspections. However, the FDA's resources are limited, and the 2015 white paper admits to an unacceptably high occurrence of problems and inspections not being a reliable predictor of quality. Companies like Valisher are stepping in to analyze every single batch of the supply chain to address these limitations. Zantac (Ranitidine), an H2 blocker drug that has been around for decades, has recently been found to contain potentially carcinogenic impurities, further emphasizing the need for robust testing and quality control measures.
Discovery of NDMA in Ranitidine: Advanced testing technology uncovered high levels of carcinogen NDMA in Ranitidine, leading to its recall despite initial skepticism
The popular heartburn medication, Ranitidine (Renédine), was found to contain high levels of a carcinogen called N-Nitrosodimethylamine (NDMA) in 2019. This discovery was made using advanced testing technology, which showed millions of nanograms of NDMA in every batch, far exceeding the FDA's maximum permissible exposure limit. The safety profile of Ranitidine was considered so high that it was commonly prescribed to pregnant women and infants. However, decades of research showed that the Ranitidine molecule was unstable and could easily degrade into NDMA. Despite initial skepticism, further investigation confirmed the findings, leading to the eventual recall of Ranitidine products. This incident highlights the importance of rigorous testing and ongoing research to ensure the safety of commonly used medications.
Discovery of NDMA in Ranitidine: A Widespread Issue: Ranitidine, a common heartburn medication, was found to contain high levels of NDMA, a potential carcinogen. The reaction forming NDMA from Ranitidine is very efficient, potentially up to 10%, and not limited to one manufacturer or batch.
The team discovered high levels of a potential carcinogen, NDMA, in various brands and manufacturers of the drug Ranitidine, not just in one specific bottle or manufacturer. The only explanation for the presence of NDMA in such large quantities was that the drug itself was reacting and forming NDMA. This was a significant finding because NDMA is a very small and volatile molecule, and the conversion of Ranitidine to NDMA is very efficient, potentially up to 10%. The discovery of NDMA in Ranitidine was concerning from a chemistry perspective, as it suggested that the drug was unstable and could form a carcinogen in the body. The team's extensive testing confirmed that the problem was not limited to one manufacturer or batch, but rather was an inherent issue with the drug itself.
NDMA's Potential to Cause Cancer: Despite trace amounts in medications, NDMA's carcinogenic properties, shown in animal studies, could potentially lead to thousands of cancer cases.
NDMA, a small molecule commonly found in certain medications, is extremely unstable and can convert into this potentially carcinogenic substance in a very short amount of time, even with minimal exposure. Despite its small size, NDMA is a potent carcinogen that alkylates and oxidizes DNA, altering its structure and disrupting appropriate cell cycle signaling. Animal studies going back to the 1950s have shown that NDMA causes cancer in various models, both in vitro and in vivo, and the doses necessary to induce cancer in rats are well-documented. However, the doses used in animal studies are much higher than the trace amounts found in medications like Val Sartan. While the exact number of cancer cases that could result from NDMA in medications is uncertain, it is concerning that thousands of cases could potentially occur due to its carcinogenic properties. The ubiquitous use of Zantac and similar medications raises the question of where the associated body bags might be, emphasizing the importance of understanding the potential risks and implications of NDMA in our daily lives.
Understanding the Challenges of Identifying Risks with Common Substances like Zantac: Despite epidemiology's value in identifying potential health risks, interpreting studies on common substances like Zantac can be complex due to weak hazard ratios and large confidence intervals. The absence of a clear association doesn't rule out a causal relationship, but it makes it harder to establish.
While epidemiology can be a valuable tool in identifying potential health risks, especially when it comes to rare conditions or unusual exposures, it can be less clear-cut when dealing with ubiquitous substances or conditions, such as common medications like Zantac. The discussion highlighted the challenges in interpreting epidemiological studies, particularly when dealing with weak hazard ratios and large confidence intervals. The absence of a clear association between Zantac use and increased cancer risk in the studies reviewed does not necessarily rule out a causal relationship, but it does make it more difficult to establish. The ongoing research by Memorial Sloan Kettering Cancer Center is expected to provide new insights into this issue. It's important to note that the potential risks associated with Zantac use, if they exist, are likely to be smaller than those of smoking and lung cancer. However, given the widespread use of Zantac, even a modest increase in risk could have significant public health implications. The debate around the value of epidemiology in studying nutrition and other common health factors was also touched upon, with the argument being made that the ubiquity of these factors makes it more challenging to identify signals and establish causality.
Uncertain impact of Zantac on cancer risk due to limited research: The presence of N-Nitrosodimethylamine (NDMA) in Zantac and other ranitidine-containing drugs raises concerns about cancer risk, but the magnitude and specific types of cancers involved are unknown.
The true impact of Zantac and other ranitidine-containing drugs on cancer risk remains uncertain due to limited research and lack of comprehensive epidemiological studies. The presence of N-Nitrosodimethylamine (NDMA) in these drugs raises concerns, as NDMA is a known carcinogen. However, the magnitude of the risk and the specific types of cancers involved are unknown. For instance, if NDMA increases the risk of rare cancers, it may be easier to identify the cause. But if it's linked to common cancers like breast and prostate cancer, the connection would be more challenging. The Zeng and Mitch study from 2016, which revealed significant NDMA exposure from a single Zantac pill, was eye-opening but did not receive more attention. This could be due to various reasons, including the researchers' backgrounds in environmental sciences and the lack of awareness in the medical community about the potential risks of NDMA in drugs. As more data becomes available, it's crucial to investigate the long-term health effects of NDMA exposure from ranitidine and other drugs.
Discovery of NDMA in Drinking Water and its Health Risks: Researchers discovered an enzyme, DDH1, which contributes to the formation of NDMA in the body, highlighting its toxicity and potential health risks despite cleanup efforts.
The discovery of N-Nitrosodimethylamine (NDMA) in drinking water, originating from a rocket fuel plant, sparked decades of research into the potential health risks of this well-known carcinogen. Researchers, including Bill Mitch, found that even after cleanup efforts, low levels of NDMA were still present in various cities. This led to the identification of an enzyme, DDH1, which plays a role in the formation of NDMA in the body. The discovery of this biological link, combined with previous research on NDMA formation in the stomach, paints a compelling picture of Renita as a toxic molecule in the human body. The FDA's initial response to this discovery, made public on September 13, 2022, downplayed the potential risks, but researchers felt it was crucial to publish their findings in a citizen petition, including the alarming chemistry and biology findings, as well as epidemiological data, to raise awareness of the issue.
Rinitidine's Instability Leads to NDMA Contamination: Despite regulatory actions in some countries, the FDA has yet to recall or ban Rinitidine due to its inherent instability leading to NDMA contamination, posing a risk to consumers.
The unstable nature of the drug Rinitidine makes it prone to forming NDMA, a potentially harmful substance, regardless of the manufacturer or production method. Countries around the world, including Canada, have taken action to recall or ban the drug following this discovery. The FDA has the authority to request recalls or even ban the drug in the US, but has yet to do so. Some countries, like Canada, have taken a stronger stance based on the evidence of the drug's instability, while others have focused on specific manufacturers with reported contamination. The FDA has challenged the testing method used to detect NDMA in Rinitidine, but the evidence suggests that the drug itself is inherently unstable and poses a significant risk to consumers.
Study finds high levels of NDMA from renitidine at body temperature: A study found high levels of NDMA, a potential carcinogen, from renitidine when tested at body temperature, challenging the FDA's analysis method and raising concerns about drug safety
Even mild heat, which is generally harmless for most other molecules, can lead to the formation of N-Nitrosodimethylamine (NDMA) from the drug renitidine. This was highlighted in a study by Zang and Mitch, which suggested that the degradation of renitidine into NDMA could occur without heat. The FDA has not specifically commented on this study. However, Valcher, in their citizen's petition, suspects that the high temperature used in the FDA's analysis method for NDMA might be causing an efficient reaction of generating NDMA from renitidine. Valcher developed a new method to analyze the reaction at body temperature and found high levels of NDMA in simulated gastric fluid conditions. This method involved putting a pill of Zantec into a bath modeled after gastric secretion and analyzing it using a low-temperature GCMS. While the low-temperature GCMS is less sensitive, the high levels of NDMA in the study made it detectable. The GCMS cannot be run at 37 degrees Celsius directly, but the sample can be analyzed at that temperature in a low-temperature GCMS profile. This is important as the NDMA levels found in the study were very high, and the sensitivity of the GCMS at 37 degrees Celsius is sufficient to detect it. The debate now lies in the details of the analysis methods and their sensitivity.
Renidine's Instability and Formation of Harmful Byproduct NDMA: Renidine's instability leads to formation of harmful byproduct NDMA, posing increased cancer risk, despite FDA's decision not to recall the drug.
The stability of Renidine, a drug used in Zantac and its generic versions, has been called into question due to the formation of potentially harmful byproduct NDMA. The instability of Renidine was confirmed through clinical studies, which showed significant amounts of NDMA in human urine. The formation of NDMA is not an artifact of instrumentation or temperature contamination, but rather an inherent property of the drug itself. The risk of continuing to use this drug, which has alternatives, is asymmetric, with the potential downside of increased cancer risk far outweighing the upside of doing nothing. The FDA is making a significant bet by not recalling the drug, and the potential consequences of being wrong could be severe. The discussion about the role of the FDA's chief risk officer in this decision-making process is an important one that should be had.
Taking Action Against Harmful Drugs: A Citizen's Guide: Citizens can protect themselves from harmful drugs like Zantac by taking action, such as stopping use upon advice, petitioning the FDA, and advocating for changes in regulations or manufacturing processes. The discovery of NDMA in Zantac and its potential environmental impact highlights the importance of individual action and regulatory oversight.
Individuals can take action to protect themselves from potential harm caused by drugs like Zantac, even if they don't have direct communication with regulatory agencies like the FDA. When concerns about Zantac arose, a laboratory discovered three patients taking the drug and advised them to stop using it. While citizens can submit petitions to the FDA, the number of petitions and their impact on regulatory decisions can vary. It's important to note that the FDA sets limits for harmful substances based on potential cancer risks over long periods. The discovery of NDMA in Zantac and its potential formation in wastewater treatment plants has raised concerns about the drug's environmental impact. Ultimately, individuals can take steps to minimize their exposure to potentially harmful drugs and advocate for changes in regulations or manufacturing processes.
Properly disposing of unused medication: Improper disposal of unused medication can harm the water system and potentially cause harm. Return unused medication to a pharmacy or disposal facility for safe disposal.
If you're disposing of unused medication, particularly renitidine, it's crucial not to flush it down the toilet or throw it in the trash. Instead, return it to a pharmacy or medication disposal facility to ensure proper disposal. This is important because improper disposal can lead to the medication entering the water system and potentially causing harm. Pharmacies like Walmart will take back the medication and even offer a refund. This issue highlights the importance of proper medication disposal and raises questions about the decision-making processes of regulatory bodies like the FDA. While the FDA is an essential organization, there are concerns about the safety and quality of medications in the system, and it's crucial to work together to ensure that every patient receives a high-quality medication. As always, it's important to consult with healthcare professionals for any medical concerns and seek professional advice before making any decisions regarding medications.
