Optimal Health and the Synthesis of Vitamin C

Diary entry by Linus Pauling, 1980. The text reads: “L[inus] P[auling] / Found enzymes enthralling / He was filled with glee / By Vitamin C”

[Reading Cameron and Pauling’s Cancer and Vitamin C, part 4 of 9]

In their ambitious 1979 book, Cancer and Vitamin C, Ewan Cameron and Linus Pauling argued that vitamin C possessed the ability to cure cancer. As remarkable as this suggestion was, in some respects it was almost secondary to the broader biological role that Pauling and Cameron assigned to the vitamin. As they made clear in their book, much of vitamin C’s importance could be attributed to the special way that it is made by most animals…not including ourselves.

As animals, including humans, have evolved, they have lost the ability to internally synthesize certain vital nutrients, which must now be obtained through diet alone. That said, nearly every being in the animal kingdom has retained the ability to synthesize its own vitamin C. In fact, humans are among a very small subset of animals who have lost this ability over evolutionary time, such that all of our vitamin C needs must now be met through diet. If a person does not meet this dietary need, they will develop scurvy, grow sick and eventually die. Therefore, it is paramount that humans regularly consume a baseline amount of vitamin C.

In addition to vitamin C, humans also cannot synthesize vitamins A, B1, B2, B6, and niacin, all of which are also essential for life. A deficiency in niacin, for example, can lead to pellagra, a primary disease of the skin which can result in death. Likewise, a deficiency in vitamin B1 can manifest as beriberi, a potentially fatal disease of the nervous system. But even though the absence of these nutrients will usher in dire consequences, humans have lost their ability to produce them internally.

Why is this so? The basic prevailing theory is that even though these nutrients are vital for life, food-based sources have historically been so plentiful that there was no need for the nutrients to be produced “in house.” Moreover, from an evolutionary perspective, obtaining a nutrient from a food source, rather than through self-synthesis, offers significant advantages, since it can require a lot of energy to internally produce nutrition. Once freed from the burden of self-synthesis, an organism becomes capable of applying that store of energy toward other activities.

But vitamin C seems to be a special case. Despite the evolutionary advantages of obtaining nutrition from food sources, every studied animal on Earth continues to synthesize it internally except for the following: humans, primates, guinea pigs, one species of fruit eating bat, a South Asian bird called the red vented bulbul, some grasshoppers, and fish in the trout family. For Pauling and Cameron, the tenacity with which animals have held on to the ability to produce their own vitamin C was further proof of its importance.

So again, why not humans too? Why have we lost this ability? Pauling and Cameron believed it was due to an evolutionary quirk.

As we have noted, there are evolutionary advantages to losing the ability to synthesize vitamin C. If two animals are competing for resources, the animal that is not also preoccupied with the internal process of generating its own nutrition will theoretically outcompete an opponent that is hamstrung with that energy burden. Pauling and Cameron believed that, at some point in the past, a mutant human ancestor who could not synthesize its own vitamin C successfully outcompeted other human ancestors, and was able to do so because, at that time – around 50 million years ago – its environment was abundant in vitamin C-rich foods. As the mutant bred and passed along its genetics to its progeny, its traits continued to outcompete, out-mate, and eventually eliminate vitamin C-synthesizing humans altogether. Pauling and Cameron posited that a similar situation arose with other animals, including primates, who have also lost their ability to synthesize vitamin C.

And while that idea makes intuitive sense, one still wonders why nearly all other animals have retained their capacity for vitamin C synthesis, even while losing the ability to internally produce other nutrients. The answer, according to Pauling and Cameron, is two-fold. Point one is that vitamin C is objectively important, and this special importance meant that animals tended to retain the ability to synthesize it. Crucially for humans, point two is that animals’ true need for vitamin C is far greater than what can be obtained through diet alone. In this sense, even though the human mutants were able to outcompete their synthesizing foes for a time by obtaining vitamin C through diet, maintaining that diet was not sustainable for a growing population, and perhaps the mutants never truly obtained enough vitamin C after all.

Pauling and Cameron were convinced that humans were underdosing their vitamin C, and doing so in part because of the guidance being provided by the very agency charged with providing accurate information on nutritional needs. The Recommended Daily Allowance (RDA) provided by the United States Food and Drug Administration (FDA) serves as a standard for the amount of a given nutrient that one should consume per day to maintain their health. Pauling and Cameron believed that the RDA chronically underestimated the true daily needs for specific nutrients; the recommendation for vitamin B1, for example, was about 1.5 times below optimum in their minds. In the case of vitamin C however, Pauling and Cameron believed the RDA to have been grossly underestimated at about 200 times below optimum daily need. Where once the FDA was recommending 60 mg of the nutrient per day, (bumped up to 90 mg in the year 2000) Pauling and Cameron pushed for 12,000 mg.

To determine the optimal dose of vitamin C for humans, Pauling and Cameron looked at how much vitamin C other animals synthesize, and how much dietary C the mutant human ancestor might have been expected to consume on a daily basis. For this second supposition, the researchers used data on how much vitamin C is present in specific foods and what types of foods were likely predominant when the mutant edged out its competition. The outcomes of this analysis connected with observations of contemporary primates who live in climates similar to the mutant and who ingest large amounts of vitamin C daily through their diets — volumes close to the 12,000 mg that Pauling and Cameron believed to be ideal. Finally, when analyzing the amount of vitamin C that other animals synthesize, a conjecture can be drawn about the optimal quantity for humans. A 154 pound goat, for example, could be expected to synthesize 13,000 mg per day, and other animals generated quantities that were roughly proportional to the goat by body weight.

For Pauling and Cameron, the evidence from the animal kingdom further compounded the idea that vitamin C is vital for life and that large amounts of the substance are crucial for maximizing health. But because we have lost our ability to produce our own vitamin C, most humans are living in states of suboptimal health and are exposing themselves to greater risk of affliction with serious disease. And because – as we saw in our previous post – the symptoms of scurvy closely mimic those of cancer, one might draw a connection between the two, and posit that biologically insufficient vitamin C levels are a source for increasing rates of cancer.

Why Vitamin C? The Scurvy Connection

James Lind

[Reading Cancer and Vitamin C, part 3 of 9]

In their 1979 book, Cancer and Vitamin C, Ewan Cameron and Linus Pauling made clear that vitamin C was uniquely suited to fight cancer, but the duo still needed to address some unanswered questions. Namely, what was so special about vitamin C, and how did that specialness help it to fight disease?  For Pauling and Cameron, part of the answer was connected to vitamin C’s protective factor against scurvy.

By the time that they were working on their book, it had been long understood that the body could store vitamin C. It was likewise well-known that, without any new infusions, these stores would deplete and symptoms of vitamin C deficiency would begin to manifest. Scurvy is the disease that arises once the stores have dropped below a critical level, with symptoms including drops in weight, loss of teeth, bleeding gums, poor wound healing, seizures, jaundice, disorientation, and eventually death. Scurvy was quite common among sailors because the food they took with them on their long voyages often lacked adequate levels of vitamin C. These foods, which were selected because they wouldn’t spoil, generally featured biscuits and cured or salted meats. But after months at sea, eventually their vitamin C concentrations would diminish, and disease would set in.

For a long while it wasn’t well understood what the exact source of scurvy might be, though many suspected it had something to do with one’s diet. As early as 1536, French explorer Jacques Cartier found that he was able to prevent scurvy by drinking a tea made from arborvitae leaves, which was great from a practical viewpoint but still didn’t unravel the root cause of the illness. Almost two centuries later, in 1747, Scottish physician James Lind initiated a concerted effort to uncover the secret. By manipulating the diets of scurvy patients, Lind soon discovered that those who were given an orange and a lemon were cured, while others who consumed diets lacking oranges and lemons continued to decline. But what exactly was in lemons and oranges that could help stave off scurvy remained a mystery.

Almost two-hundred years passed before the secret ingredient in oranges and lemons was finally unlocked, when Albert Szent-Györgyi isolated the substance in 1928 and correctly identified it as vitamin C in 1932. As a result of Lind’s discovery and Szent- Györgyi’s subsequent work, scurvy is now an entirely preventable disease.

As they continued their review of the literature, Pauling and Cameron came to realize that there is also a connection between scurvy and cancer; a connection that was also made centuries earlier by James Lind. When Lind was conducting his scurvy work, part of his search for a cure involved performing autopsies on those who had died of the disease, and he was interested to find that many patients with scurvy also suffered from cancerous tumors. This intriguing connection between cancer and scurvy was not more fully explored at the time, because when people contracted scurvy, they typically died shortly thereafter, meaning that cancer was rarely their cause of death.

In 1954 however, a Canadian physician, W.J. McCormick, reached the conclusion that both scurvy and cancer were diseases of collagen, and that scurvy damaged cells in a manner almost identical to the changes wrought by cancer cells as they replicate. McCormick also pointed out that late-stage cancer symptoms are very similar to those of late-stage scurvy, including anemia, hemorrhaging, formation of ulcers, increases in infections, and low levels of plasma and leukocytes. These connections added weight to Pauling and Cameron’s belief that vitamin C held secrets to fighting cancer, and encouraged them to keep pressing their case.

Why Vitamin C? Cancer Fighting Properties

Ewan Cameron, Ava Helen and Linus Pauling. Glasgow, Scotland, October 1976.

[An analysis of Ewan Cameron and Linus Pauling’s book, Cancer and Vitamin C. This is part 2 of 9.]

In their 1979 book, Cancer and Vitamin C, Ewan Cameron and Linus Pauling argued that vitamin C could be used to effectively treat cancer. With such a bold claim having been issued, vitamin C now needed to do a lot of heavy lifting. More specifically, Pauling and Cameron needed to prove that vitamin C could a) effectively treat cancer and also b) do so better than other substances being used to treat and cure cancer. As such, the authors devoted nearly half of their book to exploring vitamin C’s unique properties, with particular attention naturally paid to its cancer-fighting abilities.

In doing so, Cameron and Pauling first examined known cancer-causing agents on the cellular level and then investigated how vitamin C interreacted with these agents. One such substance was the enzyme hyaluronidase. When Pauling and Cameron were writing their book, it was widely recognized that certain malignant tumors released this enzyme and that, when exposed to healthy tissues, the enzyme would break down the glycosaminoglycans, which might be likened to the “cement” that makes tissues strong. As the cement became weaker, the tissues grew more vulnerable to being penetrated by cancer cells. By extension, it was believed that hyaluronidase promoted the spread of malignant cells within the body. It was also suspected that cancer cells released a different enzyme, collagenase, which would break down the collagen in tissues, further weakening cells and making them more susceptible to disease.

Having established this, Pauling and Cameron then illustrated the role that vitamin C could play in obstructing this process. Studies had found that vitamin C naturally helps to produce a hyaluronidase inhibitor, which in effect blocks the enzyme and stops the destruction of the tissue cement. Furthermore, vitamin C is known to be a necessary component for the building of collagen, and it was proposed that increased intake of vitamin C could boost collagen production and strengthen cells even more.

When Pauling and Cameron published their first edition, some of the ideas regarding hyaluronidase and collagenase were speculative. Pauling and Cameron were also relying on their collective scientific expertise to develop a model for vitamin C’s interactions with these enzymes. Pauling was not shy about making informed inferences to explain scientific phenomena, and in the case of vitamin C and these two enzymes, his thinking appears to have been correct. Since the publication of the first edition of Cancer and Vitamin C, two different research teams have published articles (in 2001, 2004, 2010, and 2011) which found evidence that vitamin C does in fact help to inhibit hyaluronidase.

More recent research has also suggested that high levels of vitamin C generate hydrogen peroxide. While it is not clear what the exact mechanism is that causes this, it is known that hydrogen peroxide can lead to a type of cell death that turns out to be useful in the cancer fight. Most healthy cells are not impacted by hydrogen peroxide because of the presence of an enzyme, catalase, that neutralizes its impact. Cancer cells, on the other hand, are not equipped with catalase; or if they are, the amount is negligible. So it is now well-established that hydrogen peroxide can kill cancer cells, but getting sufficient quantities of hydrogen peroxide to cancer cells inside the body has proven challenging. By administering large doses of vitamin C, it is hoped that clinicians may someday be able to provide targeted hydrogen peroxide therapy to patients who could benefit from it.

While Pauling and Cameron were able to provide data-based connections between vitamin C and its ability to fight cancer, their book also includes more anecdotal ideas that support their argument. One such observation was that patients who were given vitamin C for cancer treatment tended to experience less severe side effects from chemotherapeutics than those who did not take vitamin C. Although it was hard to quantify, Pauling and Cameron noted several instances where bed-ridden patients under Cameron’s care would take vitamin C and soon be capable of moving about. Cameron also observed that patients who stopped taking vitamin C often saw their symptoms rapidly return.

More notably, several of Cameron’s patients who were given vitamin C were found to go into remission. Because of ethical concerns related to placebo trials, Cameron and Pauling did not have any controls to support their claims. However, many of the patients took no treatment other than vitamin C, and Cameron, who had been a practicing physician for many years prior to beginning work on vitamin C therapy, understood that remissions for many of these cancers was not at all common.

To further support the notion that there was something special about vitamin C, Pauling and Cameron also observed that healthy people could not tolerate as much supplemental vitamin C as could those suffering from cancer. That is to say, healthy patients could take only so much vitamin C before they began to experience side effects, such as diarrhea, than was the case with cancer patients. This anecdote suggested to the authors that cancer patients needed a large amount of vitamin C – all of it was, in effect, being used, and as such there were no negative side effects. In fact, the appropriate dosage was often determined by giving a patient as much as they could tolerate before experiencing side effects.

Pauling and Cameron knew that vitamin C helped fight cancer. They saw that their patients were getting better and, from a molecular viewpoint, the mechanisms involved made sense, even if the data wasn’t in hand to prove everything. But there was more to support vitamin C as a model substance for treating cancer, and that had to do with its connection to scurvy, which we will explore in our next post.

Reading “Cancer and Vitamin C”

[An exploration of Ewan Cameron and Linus Pauling’s influential – and controversial – 1979 book. This introductory post is part 1 of 9.]

Despite all of the research that goes into cancer, relatively little progress has been made in its treatment — at least, that was the conclusion that Linus Pauling had arrived at in the 1960s. Long interested in the subject, Pauling was frustrated that many of the treatment options that had been developed helped to prolong life, but usually failed to cure disease.

As someone who often looked first to chemistry in his search for answers, Pauling increasingly came to believe that his growing interest in the power of vitamins might hold the key to not just treating cancer but curing it. By the 1970s, Pauling had teamed up with a key collaborator, Scottish physician Ewan Cameron, and in 1979 the duo published an important book titled Cancer and Vitamin C.

Beginning in the 1960s, Pauling’s scientific gaze began to focus on the connection between the potential connection between optimal health and vitamins, and he eventually came to theorize that many diseases could be sourced to vitamin deficiencies. By extension, Pauling surmised that if a deficiency of vitamins could cause disease, then perhaps an increase in vitamins could help stave off or even reverse an illness. Doing so, however, was not merely a case of the patient taking a few supplements. Instead, Pauling reasoned that massive amounts of a vitamin were often necessary.

This approach to treating disease – commonly referred to as megadosing – blossomed into a new field, which Pauling labeled “orthomolecular medicine.” Convinced that this work had great promise, Pauling co-founded an institute devoted to advancing the research, much of which he and his collaborators published in both the scientific and popular literature. Orthomolecular medicine, in Pauling’s view, could help cure maladies ranging from the common cold to schizophrenia. And while many vitamins were of interest to Pauling, one in particular took on central importance: vitamin C.

In 1979, Pauling and Cameron completed work on Cancer and Vitamin C, a popular text in which the authors attempt to persuade their readers to agree with two basic ideas: one, that vitamin C is powerful enough to treat cancer; and two, that the treatment regimen they outline actually works. Over the next three weeks, we will explore Cameron and Pauling’s endorsement of vitamin C from three different angles. After that, we will dig into an analysis of the book itself, including important updates on new research that were incorporated into a 2018 reissue of the volume.

Vitamin C for COVID Pneumonia and More

[Part 2 of 2]

The second half of the Linus Pauling Institute’s annual Pauling Day event was devoted to a question-and-answer session with the day’s panel speakers: Anitra Carr, Alpha “Berry” Fowler, Jeanne Drisko and Maret Traber. Event moderator Alexander Michels, a researcher at LPI, fielded questions submitted by the large audience watching live on Zoom and YouTube. The conversation was dominated by intriguing work being done on vitamin C and COVID-19, though several other topics were discussed as well. Here is a synopsis of the Q&A.

How much vitamin C should we be taking?

Carr answered this question first and noted that, while a lot depends on one’s condition, studies have generally found that healthy people need about 200 mg per day. Carr added that obtaining this amount through supplements is fine, since the body will excrete any excess vitamin C that is not used, but that it is also possible to ingest this amount through fruits and vegetables alone. As mentioned by Traber in her presentation, a diet of 5-9 servings per day of fruits and vegetables will usually provide enough vitamin C. Carr added the caveat that this is only the case when at least two of those servings come from fruits or vegetables with high vitamin C concentrations; foods like kiwi fruit or oranges. Further, cooking foods decreases the bioavailability of vitamin C and should be considered when calculating one’s daily vitamin C intake.

While most panelists generally agreed with Carr, they did have some additional thoughts. Michels, the event moderator, noted that LPI recommends at least 400 mg per day, simply because most people do not know if they are in sub-optimal health or suffering from Metabolic Syndrome. Given that the 200 mg value is put forth for those who are already at optimum health, in LPI’s view it is best practice to err on the side of extra vitamin C, especially since there are virtually no side effects connected with taking a higher than necessary dose. Drisko echoed Michels’ comment and added that, because of the inherent difficulties in testing vitamin C blood plasma levels, developing an accurate assessment of need is often a challenge. In keeping once again with the idea that it is better to be safe than sorry, Drisko recommends that people go as high as they can tolerate when supplementing vitamin C. This method, which Drisko personally uses, means that intake might fluctuate from day to day, but may also yield better long-term results. Fowler agreed that supplementing is a good idea and added that he personally takes 500 mg twice per day of a buffered vitamin C, which helps to minimize some of the gastral symptoms that can arise when using higher levels of the vitamin.

Is there a difference between various forms of vitamin C?

Drisko and Carr both answered this question, and both made clear that there is no difference in terms of bioavailability from one form to another. Drisko did note that lipid-encapsulated vitamin C helps to reduce gastrointestinal symptoms and recommends its use. That said, she also cautioned that lipid-encapsulated vitamin C cannot be used in intravenous treatment.

Tell us more about the use of vitamin C in treating COVID-19.

This next question was directed initially to Fowler, who is currently running a COVID-19 and vitamin C study. Fowler explained that COVID pneumonia, which is caused by a virus, creates an infection of the airways that presents in a manner similar to sepsis. Previous research has also found that viral- and bacterial-derived sepsis present in basically the same way, and that both respond well to vitamin C infusions. Based on this, Fowler felt that there could be promise in using intravenous vitamin C to treat patients suffering from COVID pneumonia.

In Fowler’s earlier research, he found that vitamin C acts as an anti-inflammatory agent. It does so by reducing the explosion of DNA that may have escaped during illness, and that often serves as a hallmark characteristic of inflammation. Fowler has also found that vitamin C reduces tissue damage. This is important because, with COVID pneumonia in particular, the virus works to destroy lung tissue.

For his current study, patients need to be positive for COVID-19, have COVID pneumonia, and be on a ventilator. In addition to the usual standards of care for COVID pneumonia, test group patients are being given an intravenous infusion of vitamin C, with dosages based on the VCU protocol. Because the study is double blind, Fowler does not know who is in the test group, but he has already noticed a stark divide in patients’ prognosis following their treatment, with some recovering rapidly and others declining. These early observations are tantalizing and may be indicative of vitamin C making a positive impact on patients suffering from COVID-19.

Drisko also spoke about her experiences related to vitamin C treatment of COVID-19. Near the beginning of the pandemic, Drisko travelled with a team of experts to Wuhan, China, the site of the index case of the virus. In Wuhan, the team treated several nearly comatose patients with vitamin C at an infusion rate of 25-50 grams per hour; rates that are similar to the VCU protocol. These patients, who were believed to be near death, wound up recovering. More detailed information on these findings is scheduled for publication.

Michels then asked the other panelists about their impressions of vitamin C and COVID-19. In response, Carr spoke of misleading studies that have prompted a false belief that vitamin C is not effective in combatting the virus. In one example, patients were given 8 grams of vitamin C orally. As Carr explained in her prepared remarks, the bioavailability of oral vitamin C is limited by the carrying capacity of transport molecules that are found in the stomach, and is thus far less effective than is intravenous vitamin C. Regardless of this limiting factor, the study did find that symptoms shortened by about 1.2 days, but that finding was not statistically significant and the study was stopped prematurely. Carr is confident that if the trial had been designed to test IVC, it would have yielded better results. Instead, the study helped to perpetuate a pessimistic narrative surrounding vitamin C’s efficacy. As Michels added, “statistically underpowered studies are misleading people and are sadly a common thing with vitamin C.”

Next, Fowler reflected on his connection with a controversial study, the VICTUS trial, which reported a negative relationship between vitamin C and COVID-19. In this instance, doctors gave patients 1.5 g of IVC four times a day, a quantity much lower than that called for by the VCU protocol. In addition to the vitamin C, patients were given 2,000 mg per day of thiamin and 50 mg of hydrocortisone four times a day. The study did not find any significant reduction in symptoms, nor a reduction in mortality. While an author on the study, Fowler emphasized that he did not participate in its design but merely helped to administer its procedures, and he pointed out several areas for criticism. In addition to the relatively low levels of vitamin C administered, the study was privately funded, and instead of the 2,000 people the study called for, just 500 people were enrolled. While critics have cited the low number of enrollees as a primary reason for such poor results, Fowler believes it was really the low levels of vitamin C. For Fowler, 50 g really is the target range for IVC, which is what is in the VCU protocol. Michels, who agreed with Fowler, commented that with vitamin C a big lesson is that “dose matters.”

Drisko then weighed in on the issue of mis-dosing. As a long-time vitamin C researcher, Drisko is confident that there is very little risk in giving a person too much vitamin C, adding that she is soon to publish a pharmacokinetic study concluding that, when cancer patients are given vitamin C up to their tolerated dose, there is no sign of organ damage. Her study also helps to combat a pervasive myth that high doses of vitamin C lead to increased bleeding or kidney damage. While the study did find increases in patients’ calcium levels, nothing about it was alarming. (Even though vitamin C has a high osmolality, the high levels of vitamin C did not destabilize calcium levels.)

Talk about the link between vitamin C and kidney stones.

In rare instances, when people are put on IVC they can develop oxalate kidney stones. To minimize these risks, Drisko recommends that all IVC patients get their urine tested to check for signs of oxalate production, an indicator of the development of these kinds of kidney stones. But, as Drisko explained, not all kidney stones are oxalate, so having a history of kidney stones is not necessarily a contraindication for IVC. More important is the need for any practitioner delivering IVC to check their patient for an inherited G6PD enzyme deficiency, because if a person has this condition and is given IVC they can develop hemolysis and risk possible death.

Drisko and Carr also commented on the risk for kidney stones posed by oral vitamin C dosing. Both agreed that this is not something that people without a history of kidney stones need to worry about, since supplementary vitamin C doses are generally equivalent to those found in a typical diet. Carr added that many studies that have shown a connection between the development of kidney stones and vitamin C do not prove cause and effect, but rather suggest a connection. There are many factors that can lead to kidney stones, such as dehydration and diet. For Carr, the popular belief that vitamin C causes kidney stones arises from weakly supported studies that do not actually prove a connection.

Alexander Michels ended the Q&A by asking panelists to comment on the future of vitamin C research, including the funding landscape for work of this sort. Carr replied that in her experience over the past two decades, finding money for vitamin C research has not gotten much easier, but that might be changing with a greater volume of encouraging results being published. Notably, researchers have recently found that vitamin C plays a role in epigenetic mechanisms and gene regulation. These data can, in turn, help support mechanistic rationales for funding, something that has often been missing in the vitamin C field. All of that said, Carr believes that the biggest barrier to stable funding is a shared body of knowledge. Too many physicians in particular are still unaware of the importance of vitamin C, and one of her jobs as a researcher is to educate colleagues about its importance. Traber agreed and noted that it is often hard to convince practitioners to trust the evidence that vitamins are important, though as more research is published, she too is hopeful that attitudes will shift.

Vitamin C and Health: New Frontiers

[Part 1 of 2]

On February 27, 2021, the Linus Pauling Institute (LPI) at Oregon State University hosted its annual Linus Pauling Day celebration, using the occasion to also mark twenty-five years of LPI at OSU. The eponymous celebration is traditionally held on Pauling’s birthday, who on February 28, 2021 would have been 120 years old. The event this year, held a day early, was also conducted entirely over Zoom due to the COVID-19 pandemic. Because it was held in a virtual space, the event was able to attract a large audience, with moderator Alexander Michels – a research associate at LPI – noting that over 1,200 people were in attendance.

This year’s topic, “Vitamin C and Health: New Frontiers” focused on the latest research into vitamin C and its impact on human health. Four experts – Anitra Carr Ph.D., University of Otago; Alpha “Berry” Fowler III M.D., Virginia Commonwealth University; Jeanne Drisko M.D., University of Kansas; and Maret Traber Ph.D., OSU – spoke about recent trends in basic and clinical research, covering topics including cancer, sepsis, and COVID-19. The 90-minute event began with prepared comments from the speakers followed by a question-and-answer session moderated by Michels.

Event welcome slide with Emily Ho speaking at right.

LPI director Emily Ho opened the event by providing some useful background on Pauling and his contributions to vitamin C research. As Ho explained, Pauling was “a true innovator” whose research into vitamin C was not initially embraced by the scientific community, despite clear evidence of its efficacy in helping reduce infection and prevent disease. Ho also explained how Pauling viewed vitamin C as the perfect vehicle to explore ideas on orthomolecular medicine; the notion that, through the intake of “the right molecule at the right dose,” one might prevent or cure many ailments. In this, Pauling helped to “revolutionize” the connection between vitamins and health.

Following Ho’s introduction, the day’s first speaker, Anitra Carr from the University of Otago in New Zealand, began her prepared remarks. Carr has a long history of working with vitamin C. Before beginning her current position in her university’s Nutrition in Medicine Research Group, Carr worked as a researcher at LPI. In 2001, Carr’s collaboration with former LPI Director Balz Frei on vitamin C and its connection to cardiovascular health helped bring about a change in the Recommended Dietary Allowance from 60mg to the 90mg per day for healthy adults.

In her talk, Carr presented an overview of vitamin C and its relationship to fighting disease. Carr explained that most animals synthesize their own vitamin C and therefore do not require any external sources of the vitamin. But humans, along with a few other animals, lack the enzyme needed to produce their own vitamin C. As vitamin C is required by humans to sustain life – it is essential for cellular energy production, hormone and neurotransmitter synthesis, metabolic regulation and, as recently determined, gene regulation – it must be obtained entirely through the consumption of fruits and vegetables, or from supplements.

Carr also reminded audience members of Pauling’s critical role in establishing vitamin C as a viable molecule to combat disease. In the 1970s, Pauling, along with Scottish surgeon Ewan Cameron, found that intravenous vitamin C megadosing could drastically improve the prognosis for critically ill cancer patients, if not outright cure them. But this research was overshadowed by other trials conducted by the Mayo Clinic that found no changes in survival rate between a placebo group and trial group. In reviewing this history, Carr stressed that the Mayo Clinic’s trial administered vitamin C orally, not intravenously, and this difference has since been proven to be quite significant. Recent research has found that intravenous vitamin C “bypasses the regulated intestinal uptake,” meaning that a person “can get much higher levels of vitamin C” in their system when the dosing is applied intravenously. In addition to improved absorption, the intravenous approach also allows for much higher doses to be applied: present-day IV infusion bags for cancer patients contain about 70 g of vitamin C, which is equivalent to about 1,000 oranges.

From there, Carr moved on to recent vitamin C research including her own, which explores the relationship between vitamin C and colorectal cancers. Specifically, Carr and her team have biopsied colorectal tumors and found that, at their core, they contain very low levels of vitamin C. When these same patients have been dosed with intravenous vitamin C, their tumor cores show higher levels of the vitamin. This finding connects with other work suggesting that, when cancer patients have high levels of vitamin C in their tumors, their prognosis improves. This is so because “vitamin C helps white blood cells eliminate pathogens from the body.” Likewise, people who are sick often have higher blood plasma levels of vitamin C, an indication of their need for the vitamin, since any unused vitamin C is rapidly excreted throughout the body. By extension, “critically ill patients tend to have higher requirements for vitamin C.”

The next speaker was Jeanne Drisko, who spoke further on the effects that vitamin C can have on prognosis. An emeritus professor at the University of Kansas Medical Center, Drisko’s presentation focused intently on the differences between oral and intravenous vitamin C (IVC), and how these two routes of administration make big differences in the ways that vitamin C acts on the body.

As Drisko explained, for healthy people, obtaining vitamin C orally (either through diet or supplements) is usually enough to maintain proper levels. (In Drisko’s slide above, this status is indicated in green.) However, when people become sick, oral vitamin C dosing is no longer adequate. This circumstance is what Drisko calls the “primary divide” and can be seen in her chart as a progression into the redder colors. Once an individual has crossed over the primary divide, their vitamin C needs increase by orders of magnitude, from requirements in the micromolar range to requirements in the millimolar range. A jump of this sort is akin to leaping across the Grand Canyon, and not achievable through the intake of oral vitamin C. Because of the inhibitory transport molecules in the gut, oral vitamin C cannot provide the blood with millimolar levels of vitamin C, and is therefore inadequate for people who have arrived at that level of need.

In the context of IVC however, differences emerge in the way that vitamin C acts within the body, depending on the dose. In the millimolar range of IVC, vitamin C can be considered a “prodrug.” In using this type of instance, Drisko explained that vitamin C is not the actor that is creating positive health benefits, but instead is acting upon a substance that is creating the positive effects. Specifically, vitamin C (“the prodrug”) helps promote the curative powers of hydrogen peroxide (“the drug”). Vitamin C saturation can eventually reach a point where it acts as a drug, and at those levels, one crosses into the “secondary divide” where the full benefits of vitamin C can be seen. Patients can arrive at the “secondary divide” with IVC dosing of about 10 grams or more, “even up to 100 grams.” Depending on the circumstances, one can benefit from increasing up to such large doses because, as Drisko put it, “it’s a linear response; the higher the dose of IVC the higher the production of hydrogen peroxide.”

Because different metabolic changes occur depending on levels of vitamin C saturation, Drisko noted that proper dosing is a critical component of any successful IVC protocol. Drisko likened this to a scenario where a prescriber treats a MRSA patient with vancomycin, an antibiotic known to be effective with bacterial infections. The proper dose to treat MRSA is one gram every eight hours, but in the hypothetical, this doctor gives the patient just one milligram every eight hours. A prescription of this sort would necessarily mean that the patient is underdosed and will not have adequate blood levels of the antibiotic to fight MRSA. As Drisko pointed out, this scenario doesn’t mean that the vancomycin is ineffective, it just means that the wrong dose was given. As with vitamin C, “dose is critical.”

So too is the rate at which a dose is administered. From her research, Drisko has concluded that an infusion rate of 0.5-1 gram per minute – akin to about 50 grams every 1-2 hours – is ideal. And while Drisko assured her audience that these high doses are safe, there is a caveat: those with a G6PD deficiency and/or a propensity for developing oxalate kidney stones should not undergo IVC therapy because of potentially life-threatening complications. (These risk factors will be discussed in more detail in our next post).

The next presentation was delivered by Alpha “Berry” Fowler III, who spoke about the connection between vitamin C, sepsis, and COVID-19. Fowler, a professor of Medicine at Virginia Commonwealth University, has found that when people are in sepsis, their vitamin C blood plasma levels drop to alarmingly low levels that nearly approximate those found in sufferers of scurvy. This led Fowler to conclude that illness and vitamin C are linked, and that those who are critically ill are somehow using up their vitamin C at a much more rapid rate than those who are not.

Seeking to test the theory that vitamin C plays a role in disease management, Fowler received funding from the National Institutes of Health to conduct a Phase III trial titled “Vitamin C Infusion for Treatment in Sepsis-Induced Acute Lung Injury.” Fowler specifically chose to test those with lung-related sepsis due to the prevailing connection between lung disease and low vitamin C levels.

In his study, which was deployed at seven medical centers around the U.S., 170 participants were randomized, with 83 placed on a placebo and 84 enrolled in the trial. Both groups received the same standard of care for sepsis, including the use of ventilators as needed. The only difference in care was that the trial group received an infusion of vitamin C at a rate of 50mg/kg every six hours over a 96-hour period, an approach that was subsequently named the “VCU Protocol.” The research team found that those receiving vitamin C infusions had plasma levels rise from the micromolar to the millimolar level – a 6,000-fold increase. Fowler and his team then charted incidents of organ failure and death over the next five years. During this period of time, 46% of the placebo patients died, as compared to 30% of the vitamin C patients.

Buoyed by these results, Fowler is now working on expanding the initial trial to a larger scale. He is also currently involved with a study on vitamin C treatment of COVID-19 pneumonia, with 140 patients currently enrolled and using the VCU Protocol.

The last speaker of the day was Maret Traber, a nutritionist and the Ava Helen Pauling Chair at LPI. Traber’s topic was Metabolic Syndrome (METS), a designator used for a range of people who are on the verge of developing disease, including obese or pre-diabetic individuals. In the U.S., approximately 35% of adults have METS. As Traber noted, people with METS also tend to have chronically low levels of vitamin C, though why this is the case is still an open question. The good new though, is that even if people have METS, they can get satisfactory levels of vitamin C through diet alone, and don’t need to be treated with IVC. Traber recommends 5-9 servings of fruits and vegetables per day for healthy people and people with METS alike. Eating a diet of this sort will also supply adequate levels of other vitamins including vitamin E – the primary focus of Traber’s work – which can work synergistically with vitamin C to reduce free radicals in the body. 

After the panelists gave their talks, the forum was opened up to a question-and-answer session. This portion of the event will be covered in next week’s post.

Pauling’s Study of Schizophrenia: Pulling Back

ASA leaflet with Pauling’s annotations, circa 1971

[Part 9 of 9]

Throughout his long advocacy of an orthomolecular approach to mental disease, Linus Pauling weathered intense skepticism from his critics and gained support from sources both likely and not. Despite this, Pauling was not always inclined to reciprocate when asked for help by certain of his allies. One notable instance of Pauling “pulling back” concerned a request by the American Schizophrenia Association and its desire to fundraise on behalf of orthomolecular medicine.

The American Schizophrenia Association (ASA), which was initially called the American Schizophrenia Foundation and later renamed the Huxley Institute, was founded in the 1960s by Pauling’s close colleagues, Humphry Osmond and Abram Hoffer. Hoffer and Osmond served on the board as Vice-President and President respectively for a number of years, and as a favor to his friends, Pauling joined the board as well.

By 1971, the ASA was in need of funds. In an effort to raise more capital and grow the organization’s membership, ASA chairman Donald Webster began organizing a direct mail campaign. Believing Pauling to be the most “well known and respected” person on the board, Webster asked Pauling to offer his signature at the bottom of the campaign’s centerpiece letter.

Webster’s draft, however, raised some red flags. For one, Pauling felt as though the style and voice of the letter was too dissimilar from his own. He was likewise concerned about attaching his name to an offering that might be scientifically inaccurate or misleading. And he was irked by a recent experience with Executive Director Mel Mendelssohn, who had written in a publicity flyer that Pauling was “one of the few men ever to have won two Nobel Prizes.” Famously the only person to have received two unshared Nobel Prizes, Pauling took the time to write to Mendelssohn and express his feeling that this “carelessness needs to be pointed out” before coolly requesting that Mendelssohn tell him “who the other men are” who had also won two Nobel Prizes.

For all of these reasons, Pauling believed that it would be “unsatisfactory” for him to sign. As he explained in his reply to Webster, “I have taken action of this sort a few times in the past, and have also regretted it a few times.”

Webster, for his part, seemed to initially understand Pauling’s hesitation, but nonetheless was persistent. He responded by first acknowledging that “style is a highly personal” characteristic “which cannot be duplicated by another writer” and then emphasizing that his initial pass was just a draft “composed for its idea value.” Clearly Webster still felt as though the ASA’s best option for fundraising was to lean on Pauling’s celebrity.

These tactics did not convince Pauling to agree to sign the letter, but did compel him to offer a new rationale for his decision. This time around, Pauling offered that he could not participate in the letter project because of the time commitment it would require and because he was “so burdened with work […] editing the contributions to the new book Orthomolecular Psychiatry.”

Though twice spurned, Webster continued the conversation and eventually Pauling agreed to have his name used for the fundraising campaign. But this acquiescence did not allay Pauling’s concerns about the veracity of the letter’s claims. For example, a suggestion that a $25 donation could “provide a kit for diagnosing schizophrenia” seemed too high. Pauling wanted to know how expensive the kits actually were, and asked the ASA to verify the cost. About a month later he received his answer — the kits did not actually cost $25, but that total would, among other things, cover the ASA’s costs of sending samples out for laboratory testing.

Pauling was bothered by what he saw as a misrepresentation of costs and also by the ASA’s failure to divulge that they were not analyzing samples in-house. For these reasons, he once again soured on the idea of signing the letter, and wrote to the organization to retract the use of his name from the campaign. Ironically, amidst this all, the ASA sent Ava Helen Pauling a solicitation letter mentioning the $25 schizophrenia kit.

Once he had decided to sever ties with the direct mail initiative, Pauling took pains to point out all the other errors that he had found in the ASA’s letter. One passage claimed that “fifty dollars distributes a research study to ten clinics.” From experience, Pauling knew that this claim was inaccurate, noting that “this seems to me to be about ten times what it should cost to distribute reprints of a paper, even including the cost of reprints.”

By October 1971, Pauling had decided that he wanted to detangle his research from ASA support, writing in a curt letter to the board that he “would prefer not to report on the work that [I] am doing at the present time.” Though he did not elaborate much on his reasons, nor comment on the conflict about the fundraising campaign, the message was clear: the time had come for Pauling to pull back from the ASA.

Pauling’s Study of Schizophrenia: Clashes with Jean Mayer

Jean Mayer. Credit: Tufts University

[Part 8 of 9]

“I am afraid you and Jean Mayer will have to lock horns. Read the attached clipping. He is doing you a lot of harm.”

-Richard Stanton, publisher of Executive Health, to Pauling, 1976.

One of the most vocal critics of Linus Pauling’s orthomolecular approach to the treatment of schizophrenia was a popular and respected nutritionist by the name of Jean Mayer. The battle between the two, which mostly played out in public forums, was pitched and sometimes ugly.

Born in France in 1920, Jean Mayer received degrees from the University of Paris in 1939. After graduation, and with the outbreak of World War II, Mayer joined the French army and served as a second lieutenant. He was captured by German forces in 1940 but managed to escape. He then fought with the Free French and Allied forces in parts of Italy and Northern Africa; for his bravery he was awarded fourteen medals, including the Croix de Guerre, which is one of France’s highest military honors.

After the war, Mayer moved to the United States, serving as a Rockefeller Foundation fellow from 1946-1948. During this period, he also met and married an American, Elizabeth Van Huysen. He received his Ph.D. in chemistry from Yale in 1950, and went on to a faculty career at Harvard, where he remained for twenty-five years. In 1975 he left Harvard to become president of Tufts University, remaining in that post for sixteen years. He died of a heart attack in 1993.

Mayer spent much of his career focusing on nutrition, and eventually became quite well-known for this work. Perhaps most notably, Mayer correctly identified a biological link between blood glucose levels and feelings of hunger. From there, Mayer helped to popularize the idea that obesity was a “disease of civilization” caused by a variety of factors such as smoking, drinking alcohol, eating a poor diet, and failing to get enough exercise. As his profile rose, Mayer helped found the National Council on Hunger and Malnutrition, and also served as an advisor to presidents Nixon, Ford, and Carter, helping to initiate federal food assistance programs during this time.

Mayer was also deeply concerned about the intersection between malnutrition and human suffering worldwide. When the Biafran War erupted in Nigeria in 1969 for example, Mayer traveled to Africa to try and assess the needs of the starving. The report that he authored convinced President Nixon to increase food aid to the war-torn region. During later periods of regional famine, Mayer was often among the first experts called upon to assess the needs of hungry people.

Given his background, it is not surprising that Mayer took an interest in Pauling’s orthomolecular research. And the more he learned, the more he came to disagree with the approach, finding it ineffective and ultimately harmful. As he began to air his disagreements with the work, a feud emerged between the two high-profile scientists, one that would last for the better part of two decades.

Although Mayer and Pauling’s public disagreement was long-standing, the crux of the issue never really changed: Mayer did not think orthomolecular therapy worked and Pauling was certain that it did. As such, their discourse tended to revolve around efforts by Pauling to disprove what he believed to be blatant misrepresentations by Mayer.

One noteworthy exchange began with Mayer publicizing a report suggesting that orthomolecular treatment of schizophrenia increased the suicide rate of those treated. Mayer was quite well-known when he began pushing this report, and Pauling knew that its conclusions would be treated as gospel by many. As such, Pauling knew that he would need to both correct what he saw as misrepresentations and also redirect public opinion in favor of trusting orthomolecular methods.

In the opinion piece that he wrote as a rebuttal, Pauling pointed out that the report’s claim had been based on a single case study. This lone outlier, in Pauling’s view, “ha[d] very little value” and should certainly not be used to draw any broader conclusions. From there, Pauling publicly urged Mayer to avoid basing his criticisms on others’ research, but to instead assess the efficacy and safety of the research that Pauling and his colleagues had done, which included numerous double-blind studies — a far cry from the single case that Mayer had leaned on. Indeed, Pauling was keen to address the suicide issue head-on, and pressed Mayer to examine the data in one double-blind study where four placebo patients had tragically taken their own lives, with nothing of the sort being recorded for the orthomolecular patients. Pauling wrote that this data “has some significance” and could not ethically be ignored by critics like Mayer.

Mayer did not retreat in his response, illustrating his position in a letter sent to Pauling. The letter contained an anecdote in which Mayer wrote of a friend’s son who had developed suicidal schizophrenia. After an initial period of hospitalization,

his father heard of treatment of schizophrenia by large doses of vitamins, to which [Pauling’s name] was associated, removed his son from close supervision, and sent him to be treated with vitamins[…] Two weeks later the young man hanged himself.

Though a stark and compelling story, the anecdote failed in the same way as the single-case report that Mayer had previously amplified. Though Pauling had no reason to dispute the truth of what Mayer had conveyed, he again expressed fundamental disagreement with Mayer’s use of a solitary account in his campaign to discredit orthomolecular therapies.

Amidst the public back and forth, Pauling invited Mayer to attend an orthomolecular symposium being hosted at Stanford University in the summer of 1972. The invitation included offer of a $250 honorarium, plus all expenses paid. Notably, Pauling did not ask that Mayer speak at the event, instead suggesting that he participate as an attendee “and take part in the discussions.” Mayer declined the invitation, citing plans to be out of the country at the time, “probably in France.”

By the mid-1970s, Mayer’s profile had grown with the public largely through his syndicated newspaper column, in which he would often respond to subscriber-generated questions concerning health. In other instances, Mayer used the space write longer form pieces on topics that he thought relevant and useful to his readership, which sometimes meant a renewal of attacks on orthomolecular therapy.

In one such instance – an April 1975 column that appeared in the Los Angeles Times and elsewhere – Mayer criticized the notion that vitamins could be used to treat schizophrenia, citing as support the growing number of mainstream researchers who argued that orthomolecular therapy had “been thoroughly disproved.” (In this, Mayer was presumably leaning on a report authored by a National Institute of Mental Health task force that had come out against orthomolecular treatments.) In other pieces, Mayer reiterated his belief that the lack of substantial changes in positive and consistent outcomes for schizophrenia patients being treated with megavitamin doses was enough to disprove even the most ardent supporters of orthomolecular therapy.

Though the volleys would continue, there did emerge a brief moment in 1983 when Mayer and Pauling joined together in supporting the ailing Soviet scientist, Andrei Sakharov. Despite their differences, Mayer and Pauling were acutely sympathetic to the perceived cruelty that Sakharov was enduring while in exile in the city of Gorky. (modern day Nizhny Novgorod). And when a new Soviet leader, Yuri Andropov, rose to power after the death of Leonid Brezhnev, many scientists, including Mayer and Pauling, embraced the opportunity to lobby for Sakharov’s release. The tone of Pauling and Mayer’s correspondence shifts during this period, as the two scientists wrote to one another to coordinate and support this work.

The cordiality was short lived however and, pretty quickly, interactions became even more vitriolic. By 1985, Mayer was a decade into his tenure as president of Tufts University, and in this capacity was able to significantly influence the school’s Diet and Nutrition newsletter. On multiple occasions, Mayer used the publication as a personal soapbox to once again discredit Pauling and his approach to schizophrenia treatment. The January 1985 issue, for instance, featured a series of articles to this effect, an effort that Pauling found to be not only inaccurate, but also petty. In a letter to Mayer, Pauling made his feelings clear:

I am disappointed[…] I think that this is the largest collection of false and misleading statements about vitamin C that I have seen so far. Every bit of contrary evidence, no matter how feeble, that has been dug up or invented in the past seems to be mentioned here.

Mayer’s response was to further the criticism, with the next issue of the newsletter making mention that “no well-designed study has ever shown that vitamins at any level cure more psychiatric problems, including schizophrenia.” In response, Pauling wrote again to Mayer that “the statements about vitamins in relation to schizophrenia are completely wrong” and that “The impression that I have is that you are part of the group that makes little effort to discover the truth about nutrition.” Given that Mayer’s entire scientific career had been based on his expertise and devotion to the field of nutrition, Pauling’s words might be interpreted as having been particularly biting.

Though the two continued to battle in public from time to time, their conflict gradually fell from view. Regardless, the two never did arrive at any agreement on the validity of orthomolecular therapy, their feud only concluding with Mayer’s death on New Year’s Day, 1993.

Pauling’s Study of Schizophrenia: A Hearing Before the Connecticut State Senate

Linus Pauling, 1977.

[Part 7 of 9]

As we have seen, a primary objective of Linus Pauling’s work on schizophrenia was to establish the therapy as legitimate and to push it closer toward the mainstream. One opportunity to do so came about in 1977, when the Connecticut state legislature introduced to its docket two bills related to orthomolecular therapy. The legislation, which would add orthomolecular approaches to the roster of standard treatments offered to patients with mental illnesses, marked a unique opportunity for Pauling and others to prod orthomolecular treatments into the mental health mainstream.

On February 17, 1977, Pauling and five other prominent mental health researchers and practitioners, testified before the Public Health and Safety Committee at the Connecticut State Senate, providing their views on two bills that had been proposed: “Bill 5465: An Act to Provide Orthomolecular Therapy to Mental Patients;” and “Bill 5635: An Act Concerning Orthomolecular Therapy.” If passed, these two pieces of legislation would add orthomolecular medicine to the standard of care provided to patients at all of Connecticut’s state-run mental hospitals.

At the hearing, two factions – one pro and one con – identified themselves rather quickly. Pauling, along with three other people from the pro-orthomolecular camp, offered their testimonies first. And while each person spoke individually, the collective put forth a common core message: that orthomolecular medicine was safe, that the science behind the approach was sound, and that those in opposition were often unfair in their criticism.

In addition to Pauling, three others spoke in support of the bills: Bernard Rimland, Michael Lesser, and Carlton Fredericks. Rimland was a well-known psychologist from San Diego whose main area of research was autism. Lesser was a psychiatrist and president of the California Orthomolecular Society; he also served as the director of the U.S. Navy Drug Rehabilitation Program at the time of the testimony. Fredericks was a public health educator and host of a syndicated radio show where he discussed nutrition education. Two years prior to the hearing, Fredericks had been elected president of the International Academy of Preventative Medicine; he was also a founding member of the Academy of Medical Preventics.

Bernard Rimland. Credit: International Society for Orthomolecular Medicine

Among the first points that the speakers pressed was the basic idea that, as Rimland noted, “the use of vitamins and minerals in the treatment of mental disorders is by far the safest, most promising new treatment available.” Lesser reinforced this sentiment in adding that, “no one has ever successfully committed suicide using a vitamin substance.” Pauling also spoke to the issue, suggesting that “these vitamins – niacin and ascorbic acid, and the other B vitamins, pyridoxine – certainly do not have toxic side-effects, even when taken in large quantities.”

From there the speakers turned their attention to what they viewed to be invalid or undue criticism offered by a community of naysayers. Lesser pointed out that much of the negative press surrounding orthomolecular medicine had been drawn from inaccurate sources. Among these were the findings of an American Psychiatric Association task force that had relied on “classical drug research techniques” that, in Lesser’s view, “must be rejected as invalid.” Bernard Rimland added that

there is an extremely strong opposition on the part of major functions, or major persons of the medical profession, against any kind of nutritional approach toward the treatment or prevention of disease. And I think that the committee ought to be aware that when they have other people testifying, there’s going to be what I regard as a very irrational opposition; irrational and uninformed opposition to this form of treatment.

Carlton Fredericks seconded this idea, theorizing that “if we had a proposal to bring a new tranquilizer into your state institutions, there would be no problem, there would be no hearing and there would be no debate, despite the fact that tranquilizers can cause irreversible brain damage, despite the fact that they are at best palliative.” Fredericks further pointed out that when Pauling

addressed a subsection of the American Psychiatric Association in the 1960s on the subject of orthomolecular psychiatry, he was booed after he made his remarks. I cite this reluctantly but to separate the point that irrational opposition is more likely to be encountered than anything rational.

As they concluded their remarks, the speakers worked to emphasize the soundness of the science behind orthomolecular medicine. Following comments from Lesser on the seeming demonstration of “great long-term effectiveness” for the orthomolecular approach, Pauling made use of his deep understanding of the past work to argue that orthomolecular techniques had, in fact, been used for a long time. “While advances in medicine are notoriously slow,” he offered, “the cultural lag in this particular case is very aggravated, because contrary to what you have heard, orthomolecular psychiatry is not new. The Russians were using a B Complex vitamin in schizophrenia in 1943; it’s in their literature.”

After the proponents had given their testimony, the opposition had a chance to speak. During the hearing, just two people spoke against the bills, but their point of view was bolstered by several letters of opposition submitted before the hearing, most of them written by organizational representatives. These letters then became a part of the official hearing record, available for use by Senators to help them make their decision. One example letter was written by Richard Kramer, chair of the Connecticut Committee on Mental Health at the Connecticut State Medical Society. In it, he made clear that neither he nor his organization were in favor of the bills passing. In his own letter, the president of the Connecticut Hospital Association, Herbert A. Anderson, also indicated that he, along with “the great majority of psychiatrists do not support” the bills.

The two speakers who offered in-person opposition testimony were Howard Zonana, an associate professor of Psychiatry at Yale University, and Bruce Bower, an internist who worked for Hartford County Medical. Both men offered a similar, bifurcated message: 1) that orthomolecular therapy was dangerous; and 2) that the bills, if passed, would force physicians to kowtow to patients’ whims, even if their treatment requests were medically unethical or contraindicated.

In seeking to define orthomolecular medicine as unsafe, Bower argued that,

controversy surrounds this area because of the lack of objective scientific data demonstrating benefit [and] because of the intense anecdotal, but highly emotional basis of its popular appeal. Minimized in this furor are the well-defined results of the hazards of this form of treatment. For example, liver damage has been documented with megavitamin therapy employing nicotinic acid or vitamin B-6. Vitamin D causes elevation of blood calcium, elevation of blood pressure, kidney stones and kidney failure.

Zonana echoed Bower’s sentiments and added that vitamin B-3’s “toxic effects include jaundice, abnormal liver function, increased uric acid levels, hypotension and dermatological conditions.”

From there, the duo painted a portrait of conflicted doctor-patient interactions. If passed, the two claimed, the bills would force mental health practitioners to act unethically, by legally mandating them to use orthomolecular medicine even if it was contraindicated. “There is a dangerous precedent,” Bower argued, “which would be introduced into the practice of medicine through any statutory requirement that a physician provide orthomolecular therapy upon the demand of the patient.”

Bower further expounded that, “to give an untrained patient the legal ability to require the doctor to give ortho-molecular therapy when, in the physician’s professional judgment, it is not called for, creates a potentially counterproductive intervention in the medical management of the patient and other unnecessary point of friction in the delicate balance between the patient and the physician.” Zonana reinforced this point, stating his belief “that there is a difference in a patient electing a treatment with informed consent and a treatment being mandated for a population.”

Though both the pro and con sides of the hearing were invited to deliver prepared testimonies, Zonana and Bower were offered more time to share their remarks and, importantly, the presiding Senators asked questions of Zonana and Bower, but not of the Pauling group. The tenor and scope of these questions revealed that the Senators were in support of the Bower-Zonana position.

Bower was the first speaker to be questioned. When asked to provide sources for his claims that megavitamins are dangerous, he immediately had a source and a citation ready, noting that it had been retrieved from the “standard pharmaceutical text […] the bible.” Later, another Senator simply asked Bower to comment about vitamins, essentially offering an open invitation to continue speaking without constraint.

A different Senator asked Bower to elaborate on his fear that the bills might force “across the board decisions,” including a mandate that physicians prescribe orthomolecular treatments. In his response, Bower stated that not only was he fearful of potential ethical issues, he was also concerned that the legislation would create an environment where necessary testing and procedures would be ignored in order to comply with a legal mandate to pursue orthomolecular therapies. Bower also suggested that baseline tests for vitamin levels “themselves are controversial,” which could lead to mismanagement of dosing and further damage to the patient.

Senators approached Zonana in a similar manner and asked him similar types of questions. One of the final questions offered was, “do you, yourself, know of any miraculous cures” such as those touted by “these megavitamins or orthomolecular treatment?”

Zonana’s response? A terse and short, no. And the fate of the bills? Perhaps unsurprisingly, they did not become law.

Pauling’s Study of Schizophrenia: The Media

[Part 6 of 9]

Even in the starchiest Establishment criticism, there lurk phrases or hints that just maybe Linus and his buddies have something – if only they would get their ducks of scientific proof in line. Lest the future catch a critic out, no one wants to say Pauling is dead flat wrong.

-Barbara Yuncker, New York Post, October 25, 1974

As with the scientific community, Pauling’s work on schizophrenia experienced a mixed reception in the media, with some commenters offering acclaim and others classifying the approach as inappropriate or even harmful. Perhaps unsurprisingly, Pauling found much of the negative press to be a misrepresentation of his or his colleagues’ work, and he did not shy away from fighting back, both in public and in private. In doing so he was seeking, of course, to maintain and uphold his image as a legitimate scientific researcher, but also to guard against the derailment of a therapy that he felt had great potential for improving the lives of many patients suffering from a terrible affliction.

One notable entanglement with a publication came in 1975 and centered around a Medical World News article titled, “Megavitamins and Mental Disease: Useful Therapy or Wishful Thinking?” Pauling found many of its claims to be wildly inaccurate and wrote to the publication’s editor, Howard Cohn, to express his objections. One of Pauling’s biggest complaints was the article’s assertion that, in a two-year double-blind study conducted by Rutgers University psychologist Richard Wittenborn, schizophrenia patients treated with niacin had experienced an “alarming side effect.” In actual fact, the observed side effect was nothing more than a mild skin rash that quickly dissipated.

For Pauling, this willingness to sensationalize “probably misled some [readers] into accepting a wrong conclusion about the toxicity of niacin.” In addition, “there is no certainty that even this benign and transient effect is a side effect of niacin [because no other] psychiatrists who have given megadoses of niacin to thousands of patients over very long periods of time” had reported a similar finding. In his letter to Cohn, Pauling asked that Medical World News publish his objections as well as a retraction. The editor responded that he was unable to publish Pauling’s defense, “owing to inevitable space limitations.”

Pauling remained intent on correcting misrepresentations of orthomolecular therapy in the media, and was also keen on collecting reports that pointed out the inefficiencies of more traditional schizophrenia therapies. For example, Pauling saved and highlighted a June 27, 1979 San Francisco Chronicle piece titled, “Shock Therapy – Not as Bad as it Sounds?” Despite its title, the article’s author notes that shock therapy is oftentimes not effective, and that as many as thirty percent of treated patients “are just not having any response.” Pauling believed that his approach might offer a solution for those thirty percent, as well as many others who responded more favorably to a therapy that, regardless of its benefit, still posed the threat of multiple side effects.

There were, however, moments where the press responded more favorably to Pauling’s perspective. In 1968, shortly after Pauling published his first article on the subject, the San Diego Union reported that “one of the country’s ablest chemists” had put forth an idea that was “quite promising.” As time moved forward and criticisms began to emerged, other newspapers offered more cautiously positive assessments. In one instance, published in April 1973, a San Jose Mercury staff writer noted Pauling’s belief that the controversy surrounding his schizophrenia work would lead to “more thorough clinical tests which…will confirm [his] claims.”

Supporters also took to the papers to press their case. One reader, Rae Irene Plick, wrote to the editor of the New Jersey Star-Ledger to express dissatisfaction with recent negative coverage of Pauling’s work. Plick made clear that she had personally benefited from megadosing therapy and, as a result, knew firsthand how effective it could be. “[F]or those of us whose families have experienced success with megavitamin therapy,” she wrote, “we can only shake our heads sadly to think of all the patients who are being deprived of this modality of treatment by so-called traditional psychiatrists.”

A higher-profile writer who likewise offered support was Barbara Yuncker, an award-winning science journalist and editor. In an October 1974 New York Post piece titled “Schizophrenia: New Treatment,” Yuncker praised Pauling’s efforts. Though acknowledging that “megavitamin therapy … has never moved into the mainstream of mental illness therapy” the concept was almost two decades old and “has been adopted by a few doctors and some patients and their families with a fervor akin to that of Bible Belt Fundamentalists.” Yuncker was clear that all credit for this rise in popularity – even modest though it may be – should rest solely with Pauling and his “unquenchable gadfly energy.” Yuncker further noted that

the critics may – and do – call orthomolecular medicine offbeat, far-out, insufficiently proven experimentally, questionable in some of its methodology – in short, a bit wacky. But they can’t – and don’t – call it quackery.

The “they,” in this case, was the “Establishment,” which was firmly against Pauling. More specifically, Yuncker pointed out that federal bodies were discouraging the use of megavitamins and that the American Psychiatric Association had formally decried Pauling’s approach. But for Yuncker, what mattered most was that the research was based in legitimate science and often seemed to be effective. These were reasons enough to keep the conversation about orthomolecular psychiatry alive.