George Lundberg, MD

The Heritage Foundation sponsored and developed Project 2025 for the explicit, stated purpose of building a conservative victory through policy, personnel, and training with a 180-day game plan after a sympathetic new President of the United States takes office. To date, Project 2025 has not been formally endorsed by any presidential campaign.

More than 100 conservative organizations are said to be participating. More than 400 conservative scholars and experts have collaborated in authorship of the mandate’s 40 chapters. Chapter 14 of the “Mandate for Leadership” is an exhaustive proposed overhaul of the Department of Health and Human Services (HHS), one of the major existing arms of the executive branch of the US government. 

The mandate’s sweeping recommendations, if implemented, would impact the lives of all Americans and all healthcare workers, as outlined in the following excerpts. 
 

Healthcare-Related Excerpts From Project 2025

• “From the moment of conception, every human being possesses inherent dignity and worth, and our humanity does not depend on our age, stage of development, race, or abilities. The Secretary must ensure that all HHS programs and activities are rooted in a deep respect for innocent human life from day one until natural death: Abortion and euthanasia are not health care.”
• “Unfortunately, family policies and programs under President Biden’s HHS are fraught with agenda items focusing on ‘LGBTQ+ equity,’ subsidizing single motherhood, disincentivizing work, and penalizing marriage. These policies should be repealed and replaced by policies that support the formation of stable, married, nuclear families.”
• “The next Administration should guard against the regulatory capture of our public health agencies by pharmaceutical companies, insurers, hospital conglomerates, and related economic interests that these agencies are meant to regulate. We must erect robust firewalls to mitigate these obvious financial conflicts of interest.”
• “All National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration regulators should be entirely free from private biopharmaceutical funding. In this realm, ‘public–private partnerships’ is a euphemism for agency capture, a thin veneer for corporatism. Funding for agencies and individual government researchers must come directly from the government with robust congressional oversight.”
• “The CDC [Centers for Disease Control and Prevention] operates several programs related to vaccine safety including the Vaccine Adverse Event Reporting System (VAERS); Vaccine Safety Datalink (VSD); and Clinical Immunization Safety Assessment (CISA) Project. Those functions and their associated funding should be transferred to the FDA [Food and Drug Administration], which is responsible for post-market surveillance and evaluation of all other drugs and biological products.”
• “Because liberal states have now become sanctuaries for abortion tourism, HHS should use every available tool, including the cutting of funds, to ensure that every state reports exactly how many abortions take place within its borders, at what gestational age of the child, for what reason, the mother’s state of residence, and by what method. It should also ensure that statistics are separated by category: spontaneous miscarriage; treatments that incidentally result in the death of a child (such as chemotherapy); stillbirths; and induced abortion. In addition, CDC should require monitoring and reporting for complications due to abortion and every instance of children being born alive after an abortion.”
• “The CDC should immediately end its collection of data on gender identity, which legitimizes the unscientific notion that men can become women (and vice versa) and encourages the phenomenon of ever-multiplying subjective identities.”
• “A test developed by a lab in accordance with the protocols developed by another lab (non-commercial sharing) currently constitutes a ‘new’ laboratory-developed test because the lab in which it will be used is different from the initial developing lab. To encourage interlaboratory collaboration and discourage duplicative test creation (and associated regulatory and logistical burdens), the FDA should introduce mechanisms through which laboratory-developed tests can easily be shared with other laboratories without the current regulatory burdens.”
• “[FDA should] Reverse its approval of chemical abortion drugs because the politicized approval process was illegal from the start. The FDA failed to abide by its legal obligations to protect the health, safety, and welfare of girls and women.”
• “[FDA should] Stop promoting or approving mail-order abortions in violation of long-standing federal laws that prohibit the mailing and interstate carriage of abortion drugs.”
• “[HHS should] Promptly restore the ethics advisory committee to oversee abortion-derived fetal tissue research, and Congress should prohibit such research altogether.”
• “[HHS should] End intramural research projects using tissue from aborted children within the NIH, which should end its human embryonic stem cell registry.”
• “Under Francis Collins, NIH became so focused on the #MeToo movement that it refused to sponsor scientific conferences unless there were a certain number of women panelists, which violates federal civil rights law against sex discrimination. This quota practice should be ended, and the NIH Office of Equity, Diversity, and Inclusion, which pushes such unlawful actions, should be abolished.”
• “Make Medicare Advantage [MA] the default enrollment option.”
• “[Legislation reforming legacy (non-MA) Medicare should] Repeal harmful health policies enacted under the Obama and Biden Administrations such as the Medicare Shared Savings Program and Inflation Reduction Act.”
• “…the next Administration should] Add work requirements and match Medicaid benefits to beneficiary needs. Because Medicaid serves a broad and diverse group of individuals, it should be flexible enough to accommodate different designs for different groups.”
• “The No Surprises Act should scrap the dispute resolution process in favor of a truth-in-advertising approach that will protect consumers and free doctors, insurers, and arbiters from confused and conflicting standards for resolving disputes that the disputing parties can best resolve themselves.”
• “Prohibit abortion travel funding. Providing funding for abortions increases the number of abortions and violates the conscience and religious freedom rights of Americans who object to subsidizing the taking of life.”
• “Prohibit Planned Parenthood from receiving Medicaid funds. During the 2020–2021 reporting period, Planned Parenthood performed more than 383,000 abortions.”
• “Protect faith-based grant recipients from religious liberty violations and maintain a biblically based, social science–reinforced definition of marriage and family. Social science reports that assess the objective outcomes for children raised in homes aside from a heterosexual, intact marriage are clear.”
• “Allocate funding to strategy programs promoting father involvement or terminate parental rights quickly.”
• “Eliminate the Head Start program.”
• “Support palliative care. Physician-assisted suicide (PAS) is legal in 10 states and the District of Columbia. Legalizing PAS is a grave mistake that endangers the weak and vulnerable, corrupts the practice of medicine and the doctor–patient relationship, compromises the family and intergenerational commitments, and betrays human dignity and equality before the law.”
• “Eliminate men’s preventive services from the women’s preventive services mandate. In December 2021, HRSA [Health Resources and Services Administration] updated its women’s preventive services guidelines to include male condoms.”
• “Prioritize funding for home-based childcare, not universal day care.”
• “ The Office of the Secretary should eliminate the HHS Reproductive Healthcare Access Task Force and install a pro-life task force to ensure that all of the department’s divisions seek to use their authority to promote the life and health of women and their unborn children.”
• “The ASH [Assistant Secretary for Health] and SG [Surgeon General] positions should be combined into one four-star position with the rank, responsibilities, and authority of the ASH retained but with the title of Surgeon General.”
• “OCR [Office for Civil Rights] should withdraw its Health Insurance Portability and Accountability Act (HIPAA) guidance on abortion.”

Dr. Lundberg is Editor in Chief, Cancer Commons, and has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Heritage Foundation sponsored and developed Project 2025 for the explicit, stated purpose of building a conservative victory through policy, personnel, and training with a 180-day game plan after a sympathetic new President of the United States takes office. To date, Project 2025 has not been formally endorsed by any presidential campaign.

More than 100 conservative organizations are said to be participating. More than 400 conservative scholars and experts have collaborated in authorship of the mandate’s 40 chapters. Chapter 14 of the “Mandate for Leadership” is an exhaustive proposed overhaul of the Department of Health and Human Services (HHS), one of the major existing arms of the executive branch of the US government. 

The mandate’s sweeping recommendations, if implemented, would impact the lives of all Americans and all healthcare workers, as outlined in the following excerpts. 
 

Healthcare-Related Excerpts From Project 2025

• “From the moment of conception, every human being possesses inherent dignity and worth, and our humanity does not depend on our age, stage of development, race, or abilities. The Secretary must ensure that all HHS programs and activities are rooted in a deep respect for innocent human life from day one until natural death: Abortion and euthanasia are not health care.”
• “Unfortunately, family policies and programs under President Biden’s HHS are fraught with agenda items focusing on ‘LGBTQ+ equity,’ subsidizing single motherhood, disincentivizing work, and penalizing marriage. These policies should be repealed and replaced by policies that support the formation of stable, married, nuclear families.”
• “The next Administration should guard against the regulatory capture of our public health agencies by pharmaceutical companies, insurers, hospital conglomerates, and related economic interests that these agencies are meant to regulate. We must erect robust firewalls to mitigate these obvious financial conflicts of interest.”
• “All National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration regulators should be entirely free from private biopharmaceutical funding. In this realm, ‘public–private partnerships’ is a euphemism for agency capture, a thin veneer for corporatism. Funding for agencies and individual government researchers must come directly from the government with robust congressional oversight.”
• “The CDC [Centers for Disease Control and Prevention] operates several programs related to vaccine safety including the Vaccine Adverse Event Reporting System (VAERS); Vaccine Safety Datalink (VSD); and Clinical Immunization Safety Assessment (CISA) Project. Those functions and their associated funding should be transferred to the FDA [Food and Drug Administration], which is responsible for post-market surveillance and evaluation of all other drugs and biological products.”
• “Because liberal states have now become sanctuaries for abortion tourism, HHS should use every available tool, including the cutting of funds, to ensure that every state reports exactly how many abortions take place within its borders, at what gestational age of the child, for what reason, the mother’s state of residence, and by what method. It should also ensure that statistics are separated by category: spontaneous miscarriage; treatments that incidentally result in the death of a child (such as chemotherapy); stillbirths; and induced abortion. In addition, CDC should require monitoring and reporting for complications due to abortion and every instance of children being born alive after an abortion.”
• “The CDC should immediately end its collection of data on gender identity, which legitimizes the unscientific notion that men can become women (and vice versa) and encourages the phenomenon of ever-multiplying subjective identities.”
• “A test developed by a lab in accordance with the protocols developed by another lab (non-commercial sharing) currently constitutes a ‘new’ laboratory-developed test because the lab in which it will be used is different from the initial developing lab. To encourage interlaboratory collaboration and discourage duplicative test creation (and associated regulatory and logistical burdens), the FDA should introduce mechanisms through which laboratory-developed tests can easily be shared with other laboratories without the current regulatory burdens.”
• “[FDA should] Reverse its approval of chemical abortion drugs because the politicized approval process was illegal from the start. The FDA failed to abide by its legal obligations to protect the health, safety, and welfare of girls and women.”
• “[FDA should] Stop promoting or approving mail-order abortions in violation of long-standing federal laws that prohibit the mailing and interstate carriage of abortion drugs.”
• “[HHS should] Promptly restore the ethics advisory committee to oversee abortion-derived fetal tissue research, and Congress should prohibit such research altogether.”
• “[HHS should] End intramural research projects using tissue from aborted children within the NIH, which should end its human embryonic stem cell registry.”
• “Under Francis Collins, NIH became so focused on the #MeToo movement that it refused to sponsor scientific conferences unless there were a certain number of women panelists, which violates federal civil rights law against sex discrimination. This quota practice should be ended, and the NIH Office of Equity, Diversity, and Inclusion, which pushes such unlawful actions, should be abolished.”
• “Make Medicare Advantage [MA] the default enrollment option.”
• “[Legislation reforming legacy (non-MA) Medicare should] Repeal harmful health policies enacted under the Obama and Biden Administrations such as the Medicare Shared Savings Program and Inflation Reduction Act.”
• “…the next Administration should] Add work requirements and match Medicaid benefits to beneficiary needs. Because Medicaid serves a broad and diverse group of individuals, it should be flexible enough to accommodate different designs for different groups.”
• “The No Surprises Act should scrap the dispute resolution process in favor of a truth-in-advertising approach that will protect consumers and free doctors, insurers, and arbiters from confused and conflicting standards for resolving disputes that the disputing parties can best resolve themselves.”
• “Prohibit abortion travel funding. Providing funding for abortions increases the number of abortions and violates the conscience and religious freedom rights of Americans who object to subsidizing the taking of life.”
• “Prohibit Planned Parenthood from receiving Medicaid funds. During the 2020–2021 reporting period, Planned Parenthood performed more than 383,000 abortions.”
• “Protect faith-based grant recipients from religious liberty violations and maintain a biblically based, social science–reinforced definition of marriage and family. Social science reports that assess the objective outcomes for children raised in homes aside from a heterosexual, intact marriage are clear.”
• “Allocate funding to strategy programs promoting father involvement or terminate parental rights quickly.”
• “Eliminate the Head Start program.”
• “Support palliative care. Physician-assisted suicide (PAS) is legal in 10 states and the District of Columbia. Legalizing PAS is a grave mistake that endangers the weak and vulnerable, corrupts the practice of medicine and the doctor–patient relationship, compromises the family and intergenerational commitments, and betrays human dignity and equality before the law.”
• “Eliminate men’s preventive services from the women’s preventive services mandate. In December 2021, HRSA [Health Resources and Services Administration] updated its women’s preventive services guidelines to include male condoms.”
• “Prioritize funding for home-based childcare, not universal day care.”
• “ The Office of the Secretary should eliminate the HHS Reproductive Healthcare Access Task Force and install a pro-life task force to ensure that all of the department’s divisions seek to use their authority to promote the life and health of women and their unborn children.”
• “The ASH [Assistant Secretary for Health] and SG [Surgeon General] positions should be combined into one four-star position with the rank, responsibilities, and authority of the ASH retained but with the title of Surgeon General.”
• “OCR [Office for Civil Rights] should withdraw its Health Insurance Portability and Accountability Act (HIPAA) guidance on abortion.”

Dr. Lundberg is Editor in Chief, Cancer Commons, and has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Heritage Foundation sponsored and developed Project 2025 for the explicit, stated purpose of building a conservative victory through policy, personnel, and training with a 180-day game plan after a sympathetic new President of the United States takes office. To date, Project 2025 has not been formally endorsed by any presidential campaign.

More than 100 conservative organizations are said to be participating. More than 400 conservative scholars and experts have collaborated in authorship of the mandate’s 40 chapters. Chapter 14 of the “Mandate for Leadership” is an exhaustive proposed overhaul of the Department of Health and Human Services (HHS), one of the major existing arms of the executive branch of the US government. 

The mandate’s sweeping recommendations, if implemented, would impact the lives of all Americans and all healthcare workers, as outlined in the following excerpts. 
 

Healthcare-Related Excerpts From Project 2025

• “From the moment of conception, every human being possesses inherent dignity and worth, and our humanity does not depend on our age, stage of development, race, or abilities. The Secretary must ensure that all HHS programs and activities are rooted in a deep respect for innocent human life from day one until natural death: Abortion and euthanasia are not health care.”
• “Unfortunately, family policies and programs under President Biden’s HHS are fraught with agenda items focusing on ‘LGBTQ+ equity,’ subsidizing single motherhood, disincentivizing work, and penalizing marriage. These policies should be repealed and replaced by policies that support the formation of stable, married, nuclear families.”
• “The next Administration should guard against the regulatory capture of our public health agencies by pharmaceutical companies, insurers, hospital conglomerates, and related economic interests that these agencies are meant to regulate. We must erect robust firewalls to mitigate these obvious financial conflicts of interest.”
• “All National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration regulators should be entirely free from private biopharmaceutical funding. In this realm, ‘public–private partnerships’ is a euphemism for agency capture, a thin veneer for corporatism. Funding for agencies and individual government researchers must come directly from the government with robust congressional oversight.”
• “The CDC [Centers for Disease Control and Prevention] operates several programs related to vaccine safety including the Vaccine Adverse Event Reporting System (VAERS); Vaccine Safety Datalink (VSD); and Clinical Immunization Safety Assessment (CISA) Project. Those functions and their associated funding should be transferred to the FDA [Food and Drug Administration], which is responsible for post-market surveillance and evaluation of all other drugs and biological products.”
• “Because liberal states have now become sanctuaries for abortion tourism, HHS should use every available tool, including the cutting of funds, to ensure that every state reports exactly how many abortions take place within its borders, at what gestational age of the child, for what reason, the mother’s state of residence, and by what method. It should also ensure that statistics are separated by category: spontaneous miscarriage; treatments that incidentally result in the death of a child (such as chemotherapy); stillbirths; and induced abortion. In addition, CDC should require monitoring and reporting for complications due to abortion and every instance of children being born alive after an abortion.”
• “The CDC should immediately end its collection of data on gender identity, which legitimizes the unscientific notion that men can become women (and vice versa) and encourages the phenomenon of ever-multiplying subjective identities.”
• “A test developed by a lab in accordance with the protocols developed by another lab (non-commercial sharing) currently constitutes a ‘new’ laboratory-developed test because the lab in which it will be used is different from the initial developing lab. To encourage interlaboratory collaboration and discourage duplicative test creation (and associated regulatory and logistical burdens), the FDA should introduce mechanisms through which laboratory-developed tests can easily be shared with other laboratories without the current regulatory burdens.”
• “[FDA should] Reverse its approval of chemical abortion drugs because the politicized approval process was illegal from the start. The FDA failed to abide by its legal obligations to protect the health, safety, and welfare of girls and women.”
• “[FDA should] Stop promoting or approving mail-order abortions in violation of long-standing federal laws that prohibit the mailing and interstate carriage of abortion drugs.”
• “[HHS should] Promptly restore the ethics advisory committee to oversee abortion-derived fetal tissue research, and Congress should prohibit such research altogether.”
• “[HHS should] End intramural research projects using tissue from aborted children within the NIH, which should end its human embryonic stem cell registry.”
• “Under Francis Collins, NIH became so focused on the #MeToo movement that it refused to sponsor scientific conferences unless there were a certain number of women panelists, which violates federal civil rights law against sex discrimination. This quota practice should be ended, and the NIH Office of Equity, Diversity, and Inclusion, which pushes such unlawful actions, should be abolished.”
• “Make Medicare Advantage [MA] the default enrollment option.”
• “[Legislation reforming legacy (non-MA) Medicare should] Repeal harmful health policies enacted under the Obama and Biden Administrations such as the Medicare Shared Savings Program and Inflation Reduction Act.”
• “…the next Administration should] Add work requirements and match Medicaid benefits to beneficiary needs. Because Medicaid serves a broad and diverse group of individuals, it should be flexible enough to accommodate different designs for different groups.”
• “The No Surprises Act should scrap the dispute resolution process in favor of a truth-in-advertising approach that will protect consumers and free doctors, insurers, and arbiters from confused and conflicting standards for resolving disputes that the disputing parties can best resolve themselves.”
• “Prohibit abortion travel funding. Providing funding for abortions increases the number of abortions and violates the conscience and religious freedom rights of Americans who object to subsidizing the taking of life.”
• “Prohibit Planned Parenthood from receiving Medicaid funds. During the 2020–2021 reporting period, Planned Parenthood performed more than 383,000 abortions.”
• “Protect faith-based grant recipients from religious liberty violations and maintain a biblically based, social science–reinforced definition of marriage and family. Social science reports that assess the objective outcomes for children raised in homes aside from a heterosexual, intact marriage are clear.”
• “Allocate funding to strategy programs promoting father involvement or terminate parental rights quickly.”
• “Eliminate the Head Start program.”
• “Support palliative care. Physician-assisted suicide (PAS) is legal in 10 states and the District of Columbia. Legalizing PAS is a grave mistake that endangers the weak and vulnerable, corrupts the practice of medicine and the doctor–patient relationship, compromises the family and intergenerational commitments, and betrays human dignity and equality before the law.”
• “Eliminate men’s preventive services from the women’s preventive services mandate. In December 2021, HRSA [Health Resources and Services Administration] updated its women’s preventive services guidelines to include male condoms.”
• “Prioritize funding for home-based childcare, not universal day care.”
• “ The Office of the Secretary should eliminate the HHS Reproductive Healthcare Access Task Force and install a pro-life task force to ensure that all of the department’s divisions seek to use their authority to promote the life and health of women and their unborn children.”
• “The ASH [Assistant Secretary for Health] and SG [Surgeon General] positions should be combined into one four-star position with the rank, responsibilities, and authority of the ASH retained but with the title of Surgeon General.”
• “OCR [Office for Civil Rights] should withdraw its Health Insurance Portability and Accountability Act (HIPAA) guidance on abortion.”

Dr. Lundberg is Editor in Chief, Cancer Commons, and has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

I don’t rightly remember when I first learned of restless legs syndrome (RLS). It was many decades ago, and I recognized that once in a while, I would be restless during sleep, tossing and turning, seeking a favorable sleeping position. I felt like I just needed to move my legs around; my gastrocnemii and hamstrings might cramp; and my torso skin might strangely “crawl” a bit, but then normal sleep would return. I never sought medical care for it and used no treatment, except moving my legs when indicated.

My trusty LLM (large language model), Bard, tells me that there are about 53,000 articles about RLS in English, of which, some 20,000 are in the primary source, peer reviewed literature. Count this as one more article. Will it make a difference? Read on and see.

For many centuries (since Sir Thomas Willis in 1672), the symptoms now grouped and categorized as RLS have been recognized and reported but were often dismissed as bizarre and unexplained. The name was applied in 1948 by Dr Karl-Axel Ekborn.

In the 1960s, in sleep labs, RLS became better studied and characterized.

Mayo Clinic describes RLS as “… compelling, unpleasant sensations in the legs or feet ... both sides of the body ... within the limb rather than on the skin ... crawling, creeping, pulling, throbbing, aching, itching, electric ... difficult to explain …” Not numbness, but a consistent desire to move the legs.

When I read about it many decades ago, I realized that I may have RLS. But then many months would pass with no recurrence, so I dismissed it as just another of those “symptoms of unknown origin” that my late friend Clifton Meador has written about so eloquently.

I am sure that a lot of people experience this, don’t understand it, and don’t consider it important enough to do anything about. Between 1% and 15% (a wide range) of Americans are believed to be affected by RLS. The cause is unknown, but it seems to run in families. It may be autosomal dominant, but no causative genes have been confirmed.
 

Treatment of RLS

Many pharmacologic and physical treatments have been tried with some success for some patients, but over time, these treatments have mostly failed.

We know how Big Pharma often operates. A company owns a drug, preferably under patent protection, but without an apparent profitable indication. They need to find a medical condition, ideally one with troublesome symptoms, that the drug might ameliorate to some degree. Armed with a plausible candidate symptom, the company embarks upon a campaign to find people who might want to take the drug. Mass communications, such as direct-to-consumer advertising, can identify large numbers of people who match to pretty much any symptoms, although many of these people never suspected they had a disease, much less a treatable one.

I figured long ago that RLS was just another of those nonspecific entities experienced by many people, making them good candidates for disease mongering.

In 2005, the marketing of GlaxoSmithKline’s (GSK’s) dopamine agonist drug Requip (ropinirole) was approved by the FDA. GSK had already undertaken an intensive promotional campaign for Requip, issuing press releases, advertising to doctors in medical journals, and advertising directly to consumers. To increase general awareness of RLS, GSK’s campaign told consumers that a “new survey reveals that a common yet underrecognized disorder-restless legs syndrome—is keeping Americans awake at night.” GSK was accused of “disease mongering,” trying to turn ordinary people into patients who needed specific drugs.

Within a year, sales of the drug had doubled, climbing from $165 million in 2005 to nearly $330 million in 2006. Soon, 4.4 million prescriptions were written annually for the drug, with sales reported to be nearly $491 million. However, the focus on RLS faded rapidly as the Requip television commercials were pulled from the airwaves following approval of generic ropinirole.

And Requip had competition. Boehringer Ingelheim manufactures pramipexole (brand name Mirapex) another dopamine agonist. Gabapentin enacarbil (marketed as Horizant by UCB Pharma) is also approved for RLS, and Pfizer’s pregabalin (brand name Lyrica) is used off-label to manage symptoms of RLS. Janssen Pharmaceuticals manufactures rotigotine, (brand name Neupro), a dopamine agonist delivered via a transdermal patch.

It is safe to say that RLS is a real clinical entity composed of clearly recognizable symptoms, with no cure and no ending, unless it is associated with iron-deficiency anemia. However, as a disease, it seems to lack etiology, pathology, pathogenesis, pathophysiology, diagnostic findings on physical examination, laboratory tests, or imaging, and any clear strategy for prevention.

Pharmacologic treatments include dopaminergic agents, benzodiazepines, opioids, anticonvulsants, alpha 2–adrenergic agonists and iron salts. Yes, you read that right; RLS is treated with a broad array of different drugs, which is usually a sign that nothing works very well. Some agents work for a while, but none seem to be the definitive solution.

Same for the physical interventions: sleep hygiene, exercise, hot or cold bathing, limb massage, vibratory or electrical stimulation of the feet, stopping caffeine before bedtime. Try everything and see if something works.
 

Taking the Sugar Challenge

Could the culprit be sugar?

Lacking clarity of scientific understanding of RLS or its treatment from an extensive clinical literature, after ascertaining that RLS is real, one might look for real-world evidence, including well-performed N-of-1 trials.

I am an antisugar guy. Read my prior Medscape columns. I practice what I preach, but sugar does taste good.

Early in November 2023, after a healthy, conservative dinner at home with some wine, I enjoyed a mini Dove bar for dessert. But I didn’t stop there.

Mini Dove bars contain 11 grams sugar. It was also just a few days after Halloween. Having had fewer trick-or-treaters than expected, we had leftovers. Snickers, Milky Ways, Twix mini bars, each with at least 20 grams of sugar.

I ate several of these not long before bedtime. Lo and behold, in the dark of that night, and continuing off and on for a few fitful hours, I had bad RLS. Shifting, tossing, turning, compulsively seeking a new sleeping position only to have to soon move again. Plus, I had repetitive leg cramps and that creepy-crawly skin sensation. An altogether unpleasant experience. Sound sleep eventually arrived, and there were no recurrences over subsequent weeks.

The classic way to determine whether a drug is causing a reaction, condition, or disease is to apply the challenge-dechallenge-rechallenge testing method.

Give the drug, the patient demonstrates the disease finding. Remove the drug, the problem disappears. Rinse and repeat three times. We pathologists first worked this out for drug-induced liver disease, such as steatosis, in the late 1960s. Blinding or double blinding in these N-of-1 situations would be nice but often not practical.

Siwert de Groot, in the Netherlands, published a very convincing use of this technique in 2023: Big-time sugar consumption for a week, then low intake of sugar for the following week, repeated three times on one patient.

Very elaborate RLS symptom reporting. I’m pretty convinced from my unintentional challenge and single dechallenge that my unusually high sugar intake resulted in RLS. I will not undergo a rechallenge, although it might be fun to binge on sucrose and see what happens.

If you are serious about identifying or treating RLS, I suggest that you incorporate the International Restless Legs Study Group Severity Rating Scale into your practice, and begin the systematic use of the dechallenge-rechallenge exclusion process for your patients with RLS. Start with sugar and see what happens. Keep records and let the world know what you discover. Be your own clinical investigator. Social media offers you abundant opportunity to share your results, whatever they may be.

How many millions of dollars would Big Pharma lose if patients with RLS just said no to sugar and it worked? Of course, humans being humans, many would probably prefer to continue to gorge on sugar, gain weight, develop diabetes, and then take medications to control their RLS symptoms. But patients ought to at least be given an informed choice.

I will be watching for your reports.

Dr. Lundberg had no disclosures.

A version of this article appeared on Medscape.com.

I don’t rightly remember when I first learned of restless legs syndrome (RLS). It was many decades ago, and I recognized that once in a while, I would be restless during sleep, tossing and turning, seeking a favorable sleeping position. I felt like I just needed to move my legs around; my gastrocnemii and hamstrings might cramp; and my torso skin might strangely “crawl” a bit, but then normal sleep would return. I never sought medical care for it and used no treatment, except moving my legs when indicated.

My trusty LLM (large language model), Bard, tells me that there are about 53,000 articles about RLS in English, of which, some 20,000 are in the primary source, peer reviewed literature. Count this as one more article. Will it make a difference? Read on and see.

For many centuries (since Sir Thomas Willis in 1672), the symptoms now grouped and categorized as RLS have been recognized and reported but were often dismissed as bizarre and unexplained. The name was applied in 1948 by Dr Karl-Axel Ekborn.

In the 1960s, in sleep labs, RLS became better studied and characterized.

Mayo Clinic describes RLS as “… compelling, unpleasant sensations in the legs or feet ... both sides of the body ... within the limb rather than on the skin ... crawling, creeping, pulling, throbbing, aching, itching, electric ... difficult to explain …” Not numbness, but a consistent desire to move the legs.

When I read about it many decades ago, I realized that I may have RLS. But then many months would pass with no recurrence, so I dismissed it as just another of those “symptoms of unknown origin” that my late friend Clifton Meador has written about so eloquently.

I am sure that a lot of people experience this, don’t understand it, and don’t consider it important enough to do anything about. Between 1% and 15% (a wide range) of Americans are believed to be affected by RLS. The cause is unknown, but it seems to run in families. It may be autosomal dominant, but no causative genes have been confirmed.
 

Treatment of RLS

Many pharmacologic and physical treatments have been tried with some success for some patients, but over time, these treatments have mostly failed.

We know how Big Pharma often operates. A company owns a drug, preferably under patent protection, but without an apparent profitable indication. They need to find a medical condition, ideally one with troublesome symptoms, that the drug might ameliorate to some degree. Armed with a plausible candidate symptom, the company embarks upon a campaign to find people who might want to take the drug. Mass communications, such as direct-to-consumer advertising, can identify large numbers of people who match to pretty much any symptoms, although many of these people never suspected they had a disease, much less a treatable one.

I figured long ago that RLS was just another of those nonspecific entities experienced by many people, making them good candidates for disease mongering.

In 2005, the marketing of GlaxoSmithKline’s (GSK’s) dopamine agonist drug Requip (ropinirole) was approved by the FDA. GSK had already undertaken an intensive promotional campaign for Requip, issuing press releases, advertising to doctors in medical journals, and advertising directly to consumers. To increase general awareness of RLS, GSK’s campaign told consumers that a “new survey reveals that a common yet underrecognized disorder-restless legs syndrome—is keeping Americans awake at night.” GSK was accused of “disease mongering,” trying to turn ordinary people into patients who needed specific drugs.

Within a year, sales of the drug had doubled, climbing from $165 million in 2005 to nearly $330 million in 2006. Soon, 4.4 million prescriptions were written annually for the drug, with sales reported to be nearly $491 million. However, the focus on RLS faded rapidly as the Requip television commercials were pulled from the airwaves following approval of generic ropinirole.

And Requip had competition. Boehringer Ingelheim manufactures pramipexole (brand name Mirapex) another dopamine agonist. Gabapentin enacarbil (marketed as Horizant by UCB Pharma) is also approved for RLS, and Pfizer’s pregabalin (brand name Lyrica) is used off-label to manage symptoms of RLS. Janssen Pharmaceuticals manufactures rotigotine, (brand name Neupro), a dopamine agonist delivered via a transdermal patch.

It is safe to say that RLS is a real clinical entity composed of clearly recognizable symptoms, with no cure and no ending, unless it is associated with iron-deficiency anemia. However, as a disease, it seems to lack etiology, pathology, pathogenesis, pathophysiology, diagnostic findings on physical examination, laboratory tests, or imaging, and any clear strategy for prevention.

Pharmacologic treatments include dopaminergic agents, benzodiazepines, opioids, anticonvulsants, alpha 2–adrenergic agonists and iron salts. Yes, you read that right; RLS is treated with a broad array of different drugs, which is usually a sign that nothing works very well. Some agents work for a while, but none seem to be the definitive solution.

Same for the physical interventions: sleep hygiene, exercise, hot or cold bathing, limb massage, vibratory or electrical stimulation of the feet, stopping caffeine before bedtime. Try everything and see if something works.
 

Taking the Sugar Challenge

Could the culprit be sugar?

Lacking clarity of scientific understanding of RLS or its treatment from an extensive clinical literature, after ascertaining that RLS is real, one might look for real-world evidence, including well-performed N-of-1 trials.

I am an antisugar guy. Read my prior Medscape columns. I practice what I preach, but sugar does taste good.

Early in November 2023, after a healthy, conservative dinner at home with some wine, I enjoyed a mini Dove bar for dessert. But I didn’t stop there.

Mini Dove bars contain 11 grams sugar. It was also just a few days after Halloween. Having had fewer trick-or-treaters than expected, we had leftovers. Snickers, Milky Ways, Twix mini bars, each with at least 20 grams of sugar.

I ate several of these not long before bedtime. Lo and behold, in the dark of that night, and continuing off and on for a few fitful hours, I had bad RLS. Shifting, tossing, turning, compulsively seeking a new sleeping position only to have to soon move again. Plus, I had repetitive leg cramps and that creepy-crawly skin sensation. An altogether unpleasant experience. Sound sleep eventually arrived, and there were no recurrences over subsequent weeks.

The classic way to determine whether a drug is causing a reaction, condition, or disease is to apply the challenge-dechallenge-rechallenge testing method.

Give the drug, the patient demonstrates the disease finding. Remove the drug, the problem disappears. Rinse and repeat three times. We pathologists first worked this out for drug-induced liver disease, such as steatosis, in the late 1960s. Blinding or double blinding in these N-of-1 situations would be nice but often not practical.

Siwert de Groot, in the Netherlands, published a very convincing use of this technique in 2023: Big-time sugar consumption for a week, then low intake of sugar for the following week, repeated three times on one patient.

Very elaborate RLS symptom reporting. I’m pretty convinced from my unintentional challenge and single dechallenge that my unusually high sugar intake resulted in RLS. I will not undergo a rechallenge, although it might be fun to binge on sucrose and see what happens.

If you are serious about identifying or treating RLS, I suggest that you incorporate the International Restless Legs Study Group Severity Rating Scale into your practice, and begin the systematic use of the dechallenge-rechallenge exclusion process for your patients with RLS. Start with sugar and see what happens. Keep records and let the world know what you discover. Be your own clinical investigator. Social media offers you abundant opportunity to share your results, whatever they may be.

How many millions of dollars would Big Pharma lose if patients with RLS just said no to sugar and it worked? Of course, humans being humans, many would probably prefer to continue to gorge on sugar, gain weight, develop diabetes, and then take medications to control their RLS symptoms. But patients ought to at least be given an informed choice.

I will be watching for your reports.

Dr. Lundberg had no disclosures.

A version of this article appeared on Medscape.com.

I don’t rightly remember when I first learned of restless legs syndrome (RLS). It was many decades ago, and I recognized that once in a while, I would be restless during sleep, tossing and turning, seeking a favorable sleeping position. I felt like I just needed to move my legs around; my gastrocnemii and hamstrings might cramp; and my torso skin might strangely “crawl” a bit, but then normal sleep would return. I never sought medical care for it and used no treatment, except moving my legs when indicated.

My trusty LLM (large language model), Bard, tells me that there are about 53,000 articles about RLS in English, of which, some 20,000 are in the primary source, peer reviewed literature. Count this as one more article. Will it make a difference? Read on and see.

For many centuries (since Sir Thomas Willis in 1672), the symptoms now grouped and categorized as RLS have been recognized and reported but were often dismissed as bizarre and unexplained. The name was applied in 1948 by Dr Karl-Axel Ekborn.

In the 1960s, in sleep labs, RLS became better studied and characterized.

Mayo Clinic describes RLS as “… compelling, unpleasant sensations in the legs or feet ... both sides of the body ... within the limb rather than on the skin ... crawling, creeping, pulling, throbbing, aching, itching, electric ... difficult to explain …” Not numbness, but a consistent desire to move the legs.

When I read about it many decades ago, I realized that I may have RLS. But then many months would pass with no recurrence, so I dismissed it as just another of those “symptoms of unknown origin” that my late friend Clifton Meador has written about so eloquently.

I am sure that a lot of people experience this, don’t understand it, and don’t consider it important enough to do anything about. Between 1% and 15% (a wide range) of Americans are believed to be affected by RLS. The cause is unknown, but it seems to run in families. It may be autosomal dominant, but no causative genes have been confirmed.
 

Treatment of RLS

Many pharmacologic and physical treatments have been tried with some success for some patients, but over time, these treatments have mostly failed.

We know how Big Pharma often operates. A company owns a drug, preferably under patent protection, but without an apparent profitable indication. They need to find a medical condition, ideally one with troublesome symptoms, that the drug might ameliorate to some degree. Armed with a plausible candidate symptom, the company embarks upon a campaign to find people who might want to take the drug. Mass communications, such as direct-to-consumer advertising, can identify large numbers of people who match to pretty much any symptoms, although many of these people never suspected they had a disease, much less a treatable one.

I figured long ago that RLS was just another of those nonspecific entities experienced by many people, making them good candidates for disease mongering.

In 2005, the marketing of GlaxoSmithKline’s (GSK’s) dopamine agonist drug Requip (ropinirole) was approved by the FDA. GSK had already undertaken an intensive promotional campaign for Requip, issuing press releases, advertising to doctors in medical journals, and advertising directly to consumers. To increase general awareness of RLS, GSK’s campaign told consumers that a “new survey reveals that a common yet underrecognized disorder-restless legs syndrome—is keeping Americans awake at night.” GSK was accused of “disease mongering,” trying to turn ordinary people into patients who needed specific drugs.

Within a year, sales of the drug had doubled, climbing from $165 million in 2005 to nearly $330 million in 2006. Soon, 4.4 million prescriptions were written annually for the drug, with sales reported to be nearly $491 million. However, the focus on RLS faded rapidly as the Requip television commercials were pulled from the airwaves following approval of generic ropinirole.

And Requip had competition. Boehringer Ingelheim manufactures pramipexole (brand name Mirapex) another dopamine agonist. Gabapentin enacarbil (marketed as Horizant by UCB Pharma) is also approved for RLS, and Pfizer’s pregabalin (brand name Lyrica) is used off-label to manage symptoms of RLS. Janssen Pharmaceuticals manufactures rotigotine, (brand name Neupro), a dopamine agonist delivered via a transdermal patch.

It is safe to say that RLS is a real clinical entity composed of clearly recognizable symptoms, with no cure and no ending, unless it is associated with iron-deficiency anemia. However, as a disease, it seems to lack etiology, pathology, pathogenesis, pathophysiology, diagnostic findings on physical examination, laboratory tests, or imaging, and any clear strategy for prevention.

Pharmacologic treatments include dopaminergic agents, benzodiazepines, opioids, anticonvulsants, alpha 2–adrenergic agonists and iron salts. Yes, you read that right; RLS is treated with a broad array of different drugs, which is usually a sign that nothing works very well. Some agents work for a while, but none seem to be the definitive solution.

Same for the physical interventions: sleep hygiene, exercise, hot or cold bathing, limb massage, vibratory or electrical stimulation of the feet, stopping caffeine before bedtime. Try everything and see if something works.
 

Taking the Sugar Challenge

Could the culprit be sugar?

Lacking clarity of scientific understanding of RLS or its treatment from an extensive clinical literature, after ascertaining that RLS is real, one might look for real-world evidence, including well-performed N-of-1 trials.

I am an antisugar guy. Read my prior Medscape columns. I practice what I preach, but sugar does taste good.

Early in November 2023, after a healthy, conservative dinner at home with some wine, I enjoyed a mini Dove bar for dessert. But I didn’t stop there.

Mini Dove bars contain 11 grams sugar. It was also just a few days after Halloween. Having had fewer trick-or-treaters than expected, we had leftovers. Snickers, Milky Ways, Twix mini bars, each with at least 20 grams of sugar.

I ate several of these not long before bedtime. Lo and behold, in the dark of that night, and continuing off and on for a few fitful hours, I had bad RLS. Shifting, tossing, turning, compulsively seeking a new sleeping position only to have to soon move again. Plus, I had repetitive leg cramps and that creepy-crawly skin sensation. An altogether unpleasant experience. Sound sleep eventually arrived, and there were no recurrences over subsequent weeks.

The classic way to determine whether a drug is causing a reaction, condition, or disease is to apply the challenge-dechallenge-rechallenge testing method.

Give the drug, the patient demonstrates the disease finding. Remove the drug, the problem disappears. Rinse and repeat three times. We pathologists first worked this out for drug-induced liver disease, such as steatosis, in the late 1960s. Blinding or double blinding in these N-of-1 situations would be nice but often not practical.

Siwert de Groot, in the Netherlands, published a very convincing use of this technique in 2023: Big-time sugar consumption for a week, then low intake of sugar for the following week, repeated three times on one patient.

Very elaborate RLS symptom reporting. I’m pretty convinced from my unintentional challenge and single dechallenge that my unusually high sugar intake resulted in RLS. I will not undergo a rechallenge, although it might be fun to binge on sucrose and see what happens.

If you are serious about identifying or treating RLS, I suggest that you incorporate the International Restless Legs Study Group Severity Rating Scale into your practice, and begin the systematic use of the dechallenge-rechallenge exclusion process for your patients with RLS. Start with sugar and see what happens. Keep records and let the world know what you discover. Be your own clinical investigator. Social media offers you abundant opportunity to share your results, whatever they may be.

How many millions of dollars would Big Pharma lose if patients with RLS just said no to sugar and it worked? Of course, humans being humans, many would probably prefer to continue to gorge on sugar, gain weight, develop diabetes, and then take medications to control their RLS symptoms. But patients ought to at least be given an informed choice.

I will be watching for your reports.

Dr. Lundberg had no disclosures.

A version of this article appeared on Medscape.com.