FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, October 12, 2023

Schizophrenia Is Chronic Encephalitis
...and Niacin Cures It

by Thomas E. Levy, MD

OMNS (October 12, 2023) Orthomolecular medicine is based on the concept that most chronic diseases are ultimately initiated, and then sustained, by the chronic deficiency of one or more vitamins, minerals, nutrients, or other natural agents. When the deficiency can be lessened, the disease improves. Conversely, the worse the deficiency and the longer it persists in the body, the more advanced and entrenched the disease becomes. What often is unclear for both the public as well as many healthcare providers is that the clinical benefits of some nutrient supplements continue to increase as the doses are increased. These doses can vastly exceed the Recommended Dietary [or Daily] Allowance (RDA) disseminated by the Food and Nutrition Board, a committee established by the United States National Academy of Sciences. Since 1997, the term Dietary Reference Intake (DRI) has been in use to describe much the same information as the RDA. The DRI recommendations have not significantly deviated from the earlier RDA recommendations. [1]

While a few nutrients can rapidly become toxic with minimally excessive intake (calcium, copper, and iron), many nutrients have little toxicity at almost any dose. [2] In general, the doses of vitamins are difficult to push to the point of clinical toxicity. However, nearly all the nutrient minerals can readily be taken to excess and result in various presentations of toxicity. Toxicity in this context refers to definable physiological damage to the supplement taker, not occasional side effects such as nausea in a sensitive stomach (niacin) or osmotic diarrhea (vitamin C or magnesium) when too much is not efficiently absorbed but accumulates in the colon instead.

However, the concern about potential toxicity keeps supplements like niacin, vitamin C, and magnesium severely underdosed, resulting in a loss of the incredible benefits they offer when optimally dosed.

Vitamin C and Magnesium Supplementation

Vitamin C is the safest of all known nutrient supplements. In fact, there has never been established any dose of vitamin C above which toxicity will reliably ensue. This is consistent with the fact that vitamin C is the molecule on which the physiology of all cells runs, and the healthy function of the body relies on having large amounts of it both inside the cells as well as outside of them. Arguably, vitamin C is the safest consumable agent in existence. Rare individuals can experience minimal side effects, but this should not be confused with any degree of cell-damaging toxicity. By contrast, too much water intake is toxic and can even result in death. [3-5]

The vitamin C RDA for older children and adults ranges from 45 to 90 mg per day. However, many people maintain a much higher level of general health when multigram supplementation is taken regularly, on the order of 100 times the RDA. Furthermore, the administration of vitamin C in doses 1,000 times the RDA are frequently given intravenously around the world for the treatment of a wide range of infections and medical conditions, with excellent effect and unrivaled safety. [6-8]

Magnesium, like all minerals, can be pushed to toxic levels of intake. However, it is almost impossible to induce toxicity with ORAL magnesium intake, as the highest levels of intake will reliably induce an osmotic diarrhea from unabsorbed magnesium reaching the colon. But when given intravenously, enough magnesium will reliably lower even the most elevated of blood pressures to hypotensive levels. In some surgeries, sufficient magnesium is infused to deliberately keep blood pressure below normal levels to help achieve hemostasis and keep the surgical field from bleeding excessively. [9-11]

Such highly-dosed infusions should only be administered in a hospitalized setting. However, the addition of a few grams of magnesium can always be added to a therapeutic vitamin/mineral IV bag and be safely infused over an hour or so in the clinic setting. In fact, the appropriate administration of magnesium by IV infusion is the best way to help restore low body levels of magnesium, especially in patients who cannot take very much orally. [12,13] Some caution and dosage adjustments need to be made by the clinician when there is decreased kidney function.

Just like vitamin C, but much less dramatically so, oral magnesium supplementation of several grams daily can be taken as long as the osmotic diarrhea is not induced. With a magnesium RDA of roughly 300 to 400 mg daily, the amounts of supplementation to keep most adults out of a significant deficiency of magnesium will be in the range of 5-fold or more of this RDA. Furthermore, very few people can reach an optimal magnesium status with oral supplementation. Rather, the practical goal is to minimize the degree of magnesium deficiency. Nevertheless, as a significant magnesium deficiency causes some diseases and makes all diseases worse, taking as much magnesium supplementation as can be readily tolerated is always a good idea. [14]

Of the 13 essential vitamins (A, C, D, E, K, B1, B2, B3, B5, B6, B7, B9, B12), increased intake and/or increased blood levels have been associated with decreased all-cause mortality for 11 of them. [15-23] Studies clearly establishing the same associations with biotin (vitamin B7) and pantothenic acid (vitamin B5) were not found. For the most part, these studies only examined vitamin intakes in the range of the RDA or DRI values, further supporting their critical support of good health even when ingested in relatively small amounts. While toxic effects can be seen with vigorous dosing of vitamin A, vitamin D, or vitamin E, the rest have RDA or DRI values that can be greatly exceeded, resulting in only improved health and blood chemistries.

Niacin: Nomenclature and Physiology

Confusion can easily arise in sorting through the literature on niacin and its derivatives. Niacin is vitamin B3. It is also known as nicotinic acid. These are all synonyms for the chemically identical substance. Niacin, vitamin B3, and nicotinic acid are completely interchangeable terms. For completeness, niacin is also rarely referred to in the literature as "vitamin PP," with the PP meaning "pellagra-preventive." Pellagra is the clinical condition that results from a severe deficiency of niacin in the body. [24]

Niacin has several vitamers. Vitamers are derivatives or related chemical substances that fulfill the same specific vitamin functions despite not being chemically identical. Niacin derivatives that qualify as vitamers include niacinamide (also known as nicotinamide or nicotinic acid amide), nicotinamide riboside, and nicotinamide mononucleotide. Referring to nicotinamide as niacinamide decreases the possibility of niacin and its vitamers as being perceived by the public as having nicotine-like properties, which it does not. All these substances promote the biosynthesis of NAD (nicotinamide adenine dinucleotide) throughout the body, and they are the primary sources of NAD. [25,26]

Large amounts of NAD are essential for optimizing the electron supply in the first of the four steps of the electron transport chain (ETC). Located along the membranes of the mitochondria inside every cell, the ETC is responsible for the production of all the ATP (adenosine triphosphate) in the body. ATP is the most important energy-providing molecule in the body. Any compromises in its production results in a decline in the healthy function of all affected tissues and organs. When there is not enough NAD present at the beginning of the ETC, sufficient ATP simply cannot be generated.

Optimizing the production of NAD for ATP synthesis in the cells is the most important function of niacin and its vitamers.

Furthermore, greater deficiencies in available NAD results in even more pronounced declines in cellular function throughout the body. Nothing is more important for optimal health than maximal amounts of intracellular ATP. [27] Low NAD levels have been recognized as a sign of aging in not only humans, but in all living cells, including those in animals and insects. [28-34]

Niacin Supplementation

Names of forms of niacin supplementation that directly fuel NAD production in the body:

• Niacin
• Niacinamide
• Nicotinamide
• Nicotinamide riboside
• Nicotinamide mononucleotide
• Inositol hexaniacinate
• Inositol hexanicotinate

Of note, niacin has an additional important property that its vitamers do not have. Reported as early as 1955, niacin has been documented to lessen the abnormal lipid metabolism that promotes atherosclerosis. [35-37] It reduces triglycerides and the lipoproteins VLDL and LDL while raising HDL, the "good" lipoprotein. [38]

If well-tolerated, niacin is the best of the supplement forms itemized above to take, as it has both the positive impact on the lipids as well as on the NAD levels in the body. It also costs less. However, niacin causes a warm to hot flushing effect in many people who supplement it. While for many people this flushing effect is either minimal or even disappears after several doses, for some people it is not tolerable. The other supplement forms noted above are largely "flush-free," and can be easily taken by nearly everyone. The downside is that the non-flushing forms do not have the positive lipid impact of unmodified niacin.

Niacin and all its vitamers profoundly impact ATP generation throughout the body, as noted above. However, like so many other powerful orthomolecular therapies, the niacin RDA and DRI is amazingly tiny, completely misleading the health seeker as to its importance and impact of much higher doses. The optimal energy-supporting doses of niacin can be 200- to 1,000-fold higher than these officially-advised doses. And other than nausea in a few individuals, side effects are decidedly uncommon. [39] Very high doses have been linked to liver toxicity, as reflected in significant liver enzyme elevation. However, minor enzyme elevation that typically resolves without discontinuation of the supplementation is not uncommon. Such enzyme increases are felt to represent a temporary increased metabolic activity in the liver cells and not inflammatory damage. [40]

In the toxin-laden, pro-oxidant environment in which we now all live, virtually everyone is deficient in the antioxidant impact provided by niacin supplementation and the NAD levels it supports. Everybody should take at least some niacin supplementation. There really does not exist a dietary regimen that can provide the NAD-producing benefits of even a minimal supplementation of niacin.

Niacin, Health, and Schizophrenia

Optimizing the production of ATP in the body is a very desirable goal. Many clinicians today regard chronic fatigue patients as having "mitochondrial dysfunction" or "mitochondrial fatigue." While decreased ATP production is uniformly present in such patients, different patients can have different reasons for that decline in production. [41] However, except for individuals with genetic deficiencies that typically cannot be completely resolved, increasing the production of ATP not only can resolve the fatigue and associated symptoms, it can also infuse the needed energy into the dysfunctional metabolic pathways to completely resolve the biochemical abnormalities that decreased the ATP production in the first place. Quite literally, this results in cellular healing. Niacin supplementation has been shown to restore healthy NAD levels (which then increase ATP production), greatly improving muscular strength in patients with mitochondrial dysfunction. [42]

Ultimately, all such dysfunction inside the cytoplasm as well as inside the mitochondria comes from increased numbers of inactivated, oxidized biomolecules relative to the numbers of normal, reduced biomolecules. This is traditionally referred to simply as increased oxidative stress. Improvements in all pathological states can be anticipated with increased ATP production, although certain conditions, such as muscle fatigue from low ATP levels, can be expected to respond even more dramatically. The heart muscle in heart failure is a classic example of a tissue severely depleted of ATP, no longer able to respond to significant exercise with a sufficiently increased production of ATP. [43]

Endomyocardial biopsies have documented that heart muscle in congestive and hypertrophic cardiomyopathies have significantly depressed levels of both ATP and NAD. [44] Normal heart muscle has the highest NAD levels in the body. [45] In both congestive and hypertrophic cardiomyopathy impaired energy metabolism has been identified. [46] Consistent with these findings, the elevation of NAD levels in different studies has been shown to improve atherosclerosis as well as different forms of heart failure, including ischemic, hypertrophic, and congestive cardiomyopathies. [47,48] In an animal study, niacin has also been shown to lessen damage in myocardial infarction. [49] Studies in both animals and humans have shown that niacinamide can lower elevated blood pressures and decrease cardiac mortality. [50,51] In a mouse model of cardiac arrest, niacinamide administration was able to normalize NAD levels and improve survival. [52]

Niacin vitamer supplementation in humans has been clearly shown to dramatically increase blood levels of NAD. [53] Not surprisingly, NAD-increasing agents, with their strong support of ATP production, are also being increasingly appreciated as being useful for both anti-aging and overall good health. [54-59] In an animal study of sepsis, probably the most advanced and dire of medical conditions, a niacin vitamer was shown to increase survival and prevent the lung and heart injury otherwise seen. [60]

Some studies indicate that lower NAD and ATP levels are the primary abnormalities that result in cancer. [61-63] In one human study, it was shown the niacinamide supplementation was effective in reducing the appearance of new skin cancers. [64] This is consistent with the pellagra-associated skin inflammation (dermatitis) seen when niacin levels are very low. [65] Higher niacin intake has been linked to decreased all-cause mortality, indicating its importance in every cell in the body. [66,67]

The clinical effectiveness of daily multigram niacinamide dosing depends on how severely the affected tissues or organs in a disease are depleted of the NAD needed to make ATP. Heart failure, while not always responsive to increased NAD production, will often respond dramatically to an improved NAD status. A significant number of patients with congestive cardiomyopathy and low cardiac output have been spared heart transplantation after adequately-dosed Coenzyme Q10 (CoQ10), another agent capable of increasing ATP production via the ETC in the mitochondria. In many of those patients, ejection fractions have increased dramatically, and all-cause mortality decreased along with an improved exercise capacity. [68-74] Also, like niacinamide, CoQ10 also improves heart failure patients with preserved ejection fractions (hypertrophic cardiomyopathy with diastolic dysfunction). [75,76]

Niacinamide has also been shown to enhance acetyl-CoA production, which in turn enhances the biosynthesis of CoQ10.

This means that niacinamide supplementation can provide the substrates needed for both NAD and CoQ10 production, directly powering two of the four steps of the ATP-producing ETC. [77,78]

Like heart muscle, the brain and central nervous system (CNS) require very high levels of ATP for normal function relative to the rest of the body. As such, having inadequate building blocks for ATP production in the body will be reflected more often and more prominently as nervous system and psychiatric disorders than other medical conditions. Many studies have indicated that niacinamide is essential for the development, growth, and maintenance of the CNS. [79-81] Furthermore, niacinamide has been shown to readily pass the blood-brain barrier in both directions, supporting its supplementation as a simple and effective approach to treating various CNS conditions. [82] Also, oral niacinamide supplementation has been shown to be very well-absorbed. [83]

Animal studies have shown that niacinamide will protect against ischemia-induced (decreased blood supply) damage in the brain and CNS. Neuronal death is reduced, and the recovery of affected sensory and motor function is improved as well. [84-87]

Significant infection protection and resolution can be seen when NAD production is optimized with niacin and several other NAD-producing agents. Sepsis recovery is supported by increased niacin levels. COVID has also been shown to resolve more rapidly with agents that help to optimize cellular ATP levels. [88-91] Improved outcomes in COVID-related acute kidney injury have been seen with niacinamide therapy. [92] Niacinamide has also been shown to lessen inflammation-induced renal failure in an animal model. [93] It has a protective effect against the pro-inflammatory toxicity of paraquat in rats. [94]

Severe niacin deficiency results in a disease known as pellagra. This syndrome has been characterized by a triad of symptoms: delirium, dermatitis, and diarrhea. More accurately, the triad should be referred to more broadly as neurocognitive, dermatological, and gastrointestinal symptoms. A substantial variation in this symptom pattern can be seen, as the circumstances resulting in a deficiency of niacin can result in a variety of other significant nutrient and micronutrient deficiencies in a given patient. [95-97] Nevertheless, the complete restoration of niacin levels in the body, along with the micronutrients supplied by a balanced diet, reliably resolves the symptoms of pellagra, including those involving the CNS.

The neurocognitive symptoms in patients with severe niacin deficiency are always present, and they can be very pronounced clinically. Both Alzheimer's disease and Parkinson's disease typically have depleted NAD levels in the affected tissue, and some of their symptoms can be lessened with increased niacin intake. [98] Other CNS symptoms, including disorientation, memory loss, confusion, dementia, poor sleep, and even frank psychosis can be seen in the severely niacin-deficient patient. [99] Of note, the statistical risk of Parkinson's disease is lessened in individuals having an increased consumption of niacin-containing foods. [100,101]

Schizophrenia is one of the most devastating of diseases, with enormous societal impact in addition to the symptoms endured along with the effective loss of a functional life in the patient. [102] Chronically increased oxidative stress defines a state of chronic inflammation in the brain (neuroinflammation). The presence of chronic inflammation in the brains of schizophrenic patients has been well-documented. [103,104] Studies have shown that schizophrenia in younger individuals can be initiated following exposure to the toxins, or pro-oxidants, encountered in prenatal exposures to infection. [105,106] Consistent with this, many cases of schizophrenia start early in life with toxin-induced abnormal neurodevelopment. [107,108]

The symptoms of schizophrenia are numerous and diverse, with some symptoms assuming a much more prominent role in one patient versus another. The bulk of the literature simply recounts the classical and well-known symptoms of schizophrenia that focus solely on brain dysfunction. Such symptoms include hallucinations, delusions with loss of contact with reality, difficulty thinking clearly, and social/emotional withdrawal, sometimes to the point of staying in a largely motionless, catatonic state. However, it has also been recognized that symptoms not directly referable to brain dysfunction are often present as well. These include the classical symptoms of pellagra, the potentially fatal condition secondary to severe niacin deficiency in the body.

The niacin deficiency in pellagra can result brain and CNS pathology manifesting as irritability, difficulty concentrating, some social withdrawal, depression and manic depression, insomnia, delirium, hallucinations, coma and even frank psychosis. Some authors have termed this "pellagroid encephalopathy." [109] Furthermore, the psychosis with associated delusions that sometimes occurs in pellagra is indistinguishable from some cases of schizophrenia. [110] These symptoms all typically resolve with adequate restoration, and maintenance, of niacin levels in the body. [111] The effective use of niacin for psychiatric symptoms has also spawned the concept of "reversible dementia," a remarkable term since dementia is generally considered to be progressive and non-resolving in nature, especially in older individuals. [112] Similarly, the close relationship between pellagra and brain dysfunction has spawned the term "niacin-respondent subset of schizophrenia." [113]

The niacin deficiency in pellagra always has symptoms of brain dysfunction, and niacin restoration treats them very effectively.

Pellagra causes significant gastrointestinal problems and symptoms. This is significant in understanding the contribution and worsening that a pellagra-related leaky gut with a pathogen-overgrown microbiome does to diseases of the CNS (and elsewhere in the body). Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), and schizophrenia have all been clearly documented to either have pathogens and/or their toxic metabolites present in the affected nervous tissue. [114-125] The damage that niacin deficiency (pellagra) does to the microbiome is a major factor in the associated neuropsychiatric problems and schizophrenia-like symptoms seen with it as well. Niacin deficiency not only results in decreased energy production in the brains of schizophrenics, it also results in the continued exposure of pathogens and/or their toxic metabolites from an abnormal gut microbiome to the CNS of those patients.

Schizophrenia most commonly appears in late adolescence or early adulthood. [126] But it can occur later in life as well. Increased intracellular oxidative stress, left unchecked, results in premature death of the affected cells. Brain volume studies have established that schizophrenic patients progressively lose gray matter and the actual physical mass of the brain over time, well beyond the deterioration seen with aging. [127-130] Microglia, the scavenger white cells of the brain, become activated in the inflammation seen in schizophrenia. [131-133] Pro-inflammatory cytokines and other inflammatory markers are also increased. [134-136] All this information leads to the following assertion:

Schizophrenia is chronic encephalitis.

Encephalitis is inflammation of the brain, typically occurring acutely in conjunction with a new viral infection precipitating widespread inflammation throughout the brain and CNS. In schizophrenia the chronically elevated inflammatory parameters indicate that ongoing inflammation is causing the signs and symptoms of schizophrenia. Schizophrenia = chronic brain inflammation = chronic encephalitis. [137] Many of the symptoms seen in acute encephalitis brain are also seen in the chronic encephalitis brain of the schizophrenic patient, including alterations in consciousness, confusion, hallucinations, and cognitive impairment. Some authors have descriptively referred to schizophrenia as "the shattered mind." [138] The steady destruction of brain tissue by the chronic inflammation also explains why schizophrenia present for years responds less readily to any nutrient or drug regimen than schizophrenia of recent onset. The chronic inflammation slowly destroying brain tissue in schizophrenia is analogous to the patient with ongoing myocarditis and death of heart muscle eventually going into congestive heart failure. The later a positive therapy is started, the less effective it will be.

The effective clinical resolution of many schizophrenics is further complicated and even impaired by the common and severe side effects seen with the drugs commonly used in its treatment. Many of these side effects are indistinguishable from many of the symptoms for which the drugs are being given. Such symptoms include restlessness, brain fog, and social withdrawal with the loss of desire to interact with others. [139] Once a schizophrenic patient has received prescription drugs for a long enough period, it can become impossible to know when the condition itself is getting worse or a drug needs to be discontinued and/or decreased in dosage. As it is, the clinical picture of an unmedicated schizophrenic patient also spans a variety of symptoms present in many different combinations. [140]

The levels of niacin in schizophrenic patients are always low, oftentimes severely so. This also means that their cellular ATP levels are significantly depressed as well. It has been clearly shown that high doses (relative to RDA or DRI recommendations) of niacin or a niacin vitamer often completely resolves schizophrenia, even in its advanced stages. And when clinical resolution is not complete, significant improvement in the major symptoms of schizophrenia is nearly always seen.

In a group of 30 acute schizophrenia patients, one gram three times daily of niacin or niacinamide were given for only 30 days, and the patients were then followed for one year. 80% of the niacin-treated group recovered versus 33% of the placebo-treated group. [141] Recovery in acute or chronic schizophrenia was only considered to have been reached when the patient

• Had complete disappearance of disease-related symptoms and signs
• Was interacting normally with family members as well as members of the community
• Became gainfully employed

Vitamin C, a perfect treatment for any condition involving chronic inflammation, was often given in a dose of 1 to 10 grams daily as well. As the primary antioxidant (anti-inflammatory agent) in the body, vitamin C should always be used to help resolve the brain inflammation of schizophrenia. [142] Much higher doses will always help, and sometimes dramatically so, especially in schizophrenia of recent onset.

While not typical, acute schizophrenia can spontaneously resolve. Presumably, the factors provoking the inflammation in the brain of those patients eventually resolve, or become much less pronounced (e.g., infection, toxin, autoimmune reaction, micronutrient depletion).

Six more double-blind, randomized and controlled clinical trials confirmed the positive impact of niacin on the recovery of schizophrenic patients. [143,144] Many of the most chronic patients (with the most structural brain damage) required this therapy for five or more years to derive clear benefits. [145] For the niacin treatment of schizophrenia, the starting dose was 1,000 mg three times daily, with the dose slowly increased to as much as 4,500 to 18,000 mg daily, depending on clinical response. For those treated with niacinamide rather than niacin, the daily dose rarely exceeded 6,000 mg due to the increased problems with nausea and stomach sensitivity. [146-148]

Dr. Abram Hoffer treated over 5,000 schizophrenic patients with this niacin protocol. No deaths ever resulted from the administration of niacin. Furthermore, consistent with the wide-ranging positive effects of niacin on NAD levels throughout the body described above, Hoffer noted improvements in many symptoms not directly attributable to schizophrenia in his niacin-treated patients. [149] He also developed a more comprehensive orthomolecular approach to schizophrenia over the course of his years in clinical practice. [150] Currently, over 85% of chronic schizophrenic patients treated with traditional measures never resolve, even if some treatment benefits are realized. Instead, they remain sick and dysfunctional for the rest of their lives when niacin is not at least a part of their treatment program.

The following can be definitively asserted:

Niacin cures acute schizophrenia most of the time. And substantial clinical improvement is the rule even when a complete cure is not realized in acute or long-standing schizophrenia.

As covered above, schizophrenia, with its close connection to pellagra, is a condition precipitated and worsened by multiple factors. A quality diet and a wide array of vitamin and mineral nutrients are mandatory for an optimal clinical response in all these patients. Several reasons account for the varied (but positive) clinical responses of schizophrenia patients treated with niacin. [151] Nevertheless, monotherapy with niacinamide has completely resolved schizophrenia. [152] As an important and non-toxic nutrient vitamin, niacin should NEVER be denied to any patient with any brain disorder, much less schizophrenia. As Dr. Hoffer put it: "Apparently the worst sin in orthodox medicine is to see a recovery for the wrong reason."

The production of ATP, the final physiological goal in the severely NAD-depleted brain (and body) of the schizophrenic patients is specifically nurtured and supported not only by niacin, but also by riboflavin, CoQ10, and methylene blue. These four agents directly power the different steps in the mitochondrial ETC needed to optimize ATP production, which directly accounts for all healing and good health. And when permanent brain damage is minimal and the symptoms are due to ongoing neuroinflammation, an excellent clinical response can be anticipated, even if a complete cure is not realized. Niacin, CoQ10, and riboflavin comprise a nutrient triad that has been shown to benefit the antioxidant status of breast cancer patients. [153-155] And even though vitamin B3 is important to everyone, its optimal dosing is achieved by few individuals. While it is literally good for everyone, it nevertheless needs to be clearly asserted that:

Everyone with any psychological or psychiatric condition should take niacin or one of its vitamers, and the dose should be maximized before considering such a condition permanent and/or unresponsive.

Currently, the standard of care in psychiatry does not include the routine administration of niacin or niacinamide for schizophrenia or any other mental or emotional disorder.

While the established standard of practice is usually sufficient to protect a physician from malpractice, deliberately avoiding the usage of niacin for schizophrenia after being exposed to much of the literature and information cited in this article nevertheless constitutes clear medical malpractice, even if it remains unadjudicated.

Healthcare practitioners have an obligation, albeit rarely-honored, to stay informed on the science of old, current, and new therapies. The benefit of niacin therapy in schizophrenia and most brain disorders is certainly not a new discovery. As with all other conditions that have been shown to clearly benefit from an orthomolecular approach to addressing vitamin, mineral, and other nutrient deficiencies, a healthcare practitioner should always be open to all legitimate scientific information that the patient might offer. If such a practitioner refuses to even review such information, and/or will not even discuss such information with the patient, it is time to find a new one.

You do not need a doctor to give you niacin, and there are no absolute contraindications to taking it. You can take it for yourself, and you can advise any friend or family member with a neurological or psychiatric condition that you have information indicating that it is often beneficial regardless of the precise diagnosis.

Recap

Niacin and its related compounds have a long history of improving the mental status of a wide variety of mental and emotional disorders. It has been shown to cure or greatly improve most cases of schizophrenia for which it is properly-dosed. These disorders are primarily caused by a severe deficiency of NAD in the ATP-generating mitochondria in all cells. The primary role of niacin is to increase NAD levels, resulting in an improved or normalized amount of cellular ATP, the most important energy-providing molecule in the body. While many other nutrients will be of benefit in schizophrenia, highly-dosed vitamin C and magnesium should always be given to further control and quell the ongoing neuroinflammation.

Pellagra, the disease established to occur after severe and long-standing niacin deficiency, typically presents with significant brain dysfunction, sometimes clinically identical to schizophrenia. Niacin administration often completely resolves such states of psychosis, further supporting the concept that NAD repletion leading to optimal ATP levels in the brain is the root cause of schizophrenia.

A chronic NAD deficiency always causes increased oxidative stress in the affected tissue. This means that schizophrenia is a chronic encephalitis, as chronic encephalitis simply means an ongoing state of neuroinflammation in the brain.

The variability in clinical response of schizophrenia to niacin therapy is primarily due to how many other nutrient deficiencies are present and whether they are properly restored. How long the schizophrenia has been present and how much irreversible brain damage (decreased brain mass) has occurred is also critical in determining how much clinical benefit is realized.

Even though the psychiatric standard of care does not include niacin therapy for schizophrenia, it can only be considered malpractice not to apply it, especially considering the enormous physical, mental, and societal impact of this dreaded disease. Opting not to use a toxic therapy that might only help a little for a relatively minor condition does not apply to niacin for schizophrenia. That reasoning is reserved for many pharmaceutical agents, not natural nutrients.

Dedicated to the work of Abram Hoffer, MD, PhD

(Dr. Thomas E Levy, an OMNS Contributing Editor, is a cardiologist, attorney, and author of 13 books. He can be reached at televymd@yahoo.com. A collection of all his OMNS articles can be easily accessed with the following link under the subheading of "Orthomolecular": https://www.tomlevymd.com/health_ebytes.php )

References

1. Institute of Medicine (US) Committee on Use of Dietary Reference Intakes in Nutrition Labeling (2003) Dietary Reference Intakes: Guiding Principles for Nutrition Labeling and Fortification. PMID: https://pubmed.ncbi.nlm.nih.gov/24967483/

2. Levy T (2023) http://orthomolecular.org/resources/omns/v19n36.shtml

3. Ferrier I (1985) Water intoxication in patients with psychiatric illness. British Medical Journal (Clinical Research Ed.) 291:1594-1596. PMID: https://pubmed.ncbi.nlm.nih.gov/3935199/

4. de Leon J, Verghese C, Tracy J et al. (1994) Polydipsia and water intoxication in psychiatric patients: a review of the epidemiological literature. Biological Psychiatry 35:408-419. PMID: https://pubmed.ncbi.nlm.nih.gov/8018788/

5. Siegel A (2015) Fatal water intoxication and cardiac arrest in runners during marathons: prevention and treatment based on validated clinical paradigms. The American Journal of Medicine 128:1070-1075. PMID: https://pubmed.ncbi.nlm.nih.gov/25910792/

6. Levy T (2002) Curing the Incurable: Vitamin C, Infectious Diseases, and Toxins, Henderson, NV: MedFox Publishing

7. Levy T (2021) http://orthomolecular.org/resources/omns/v17n28.shtml

8. Levy T, Hunninghake R (2022) http://orthomolecular.org/resources/omns/v18n14.shtml

9. Ryu J, Sohn I, Do S (2009) Controlled hypotension for middle ear surgery: a comparison between remifentanil and magnesium sulphate. British Journal of Anaesthesia 103:490-495. PMID: https://pubmed.ncbi.nlm.nih.gov/19687032/

10. Jangra K, Malhotra S, Gupta A, Arora S (2016) Comparison of quality of the surgical field after controlled hypotension using esmolol and magnesium sulfate during endoscopic surgery. Journal of Anaesthesiology, Clinical Pharmacology 32:325-328. PMID: https://pubmed.ncbi.nlm.nih.gov/27625479/

11. Juibari H, Eftekharian H Arabion H (2016) Intravenous magnesium sulfate to deliberate hypotension and bleeding after bimaxillary orthognathic surgery; a randomized double-blind controlled trial. Journal of Dentistry 17:276-282. PMID: https://pubmed.ncbi.nlm.nih.gov/27840841/

12. Woods K, Fletcher S (1994) Long-term outcome after intravenous magnesium sulphate in suspected acute myocardial infarction: the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). Lancet 343:816-819. PMID: https://pubmed.ncbi.nlm.nih.gov/7908076/

13. Shechter M, Hod H, Rabinowitz B et al. (2003) Long-term outcome of intravenous magnesium therapy in thrombolysis-ineligible acute myocardial infarction patients. Cardiology 99:205-210. PMID: https://pubmed.ncbi.nlm.nih.gov/12845247/

14. Levy T (2019) Magnesium: Reversing Disease, Henderson, NV: MedFox Publishing [For a free download of the eBook: https://mag.medfoxpub.com/]

15. Huang Y, Lee M, Wahlqvist M (2012) Prediction of all-cause mortality by B group vitamin status in the elderly. Clinical Nutrition 31:191-198. PMID: https://pubmed.ncbi.nlm.nih.gov/22071291/

16. Ricci C, Freisling H, Leitzmann M et al. (2020) Diet and sedentary behaviour in relation to cancer survival. A report from the national health and nutrition examination survey linked to the U.S. mortality registry. Clinical Nutrition 39:3489-3496. PMID: https://pubmed.ncbi.nlm.nih.gov/32229168/

17. Imdad A, Mayo-Wilson E, Haykal M et al. (2022) Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. The Cochrane Database of Systematic Reviews 3:CD008524. PMID: https://pubmed.ncbi.nlm.nih.gov/35294044/

18. Shea M, Barger K, Booth S et al. (2022) Vitamin K status, all-cause mortality, and cardiovascular disease in adults with chronic kidney disease: the Chronic Renal Insufficiency Cohort. The American Journal of Clinical Nutrition 115:941-948. PMID: https://pubmed.ncbi.nlm.nih.gov/34788785/

19. Wang J, Fan J, Yang Y et al. (2022) Vitamin D status and risk of all-cause and cause-specific mortality in osteoarthritis patients: results from NHANES III and NHANES 2001-2008. Nutrients 14:4629. PMID: https://pubmed.ncbi.nlm.nih.gov/36364891/

20. Xu K, Peng R, Zou Y et al. (2022) Vitamin C intake and multiple health outcomes: an umbrella review of systematic reviews and meta-analyses. International Journal of Food Sciences and Nutrition 73:588-599. PMID: https://pubmed.ncbi.nlm.nih.gov/35291895/

21. Hong Y, Zhou Z, Zhang N et al. (2022) Association between plasma vitamin B5 levels and all-cause mortality: a nested case-control study. Journal of Clinical Hypertension 24:945-954. PMID: https://pubmed.ncbi.nlm.nih.gov/35699663/

22. Liu Y, Geng T, Wan Z et al. (2022) Associations of serum folate and vitamin B12 levels with cardiovascular disease mortality among patients with type 2 diabetes. JAMA Network Open 5:e2146124. PMID: https://pubmed.ncbi.nlm.nih.gov/35099545/

23. Xu Q, Qian X, Sun F et al. (2023) Independent and joint associations of dietary antioxidant intake with risk of post-stroke depression and all-cause mortality. Journal of Affective Disorders 322:84-90. PMID: https://pubmed.ncbi.nlm.nih.gov/36372128/

24. Holubiec P, Leonczyk M, Staszewski F et al. (2021) Pathophysiology and clinical management of pellagra-a review. Folia Medica Cracoviensia 61:125-137. PMID: https://pubmed.ncbi.nlm.nih.gov/34882669/

25. Fricker R, Green E, Jenkins S, Griffin S (2018) The influence of nicotinamide on health and disease in the central nervous system. International Journal of Tryptophan Research 11:1-11. PMID: https://pubmed.ncbi.nlm.nih.gov/29844677/

26. Vignier N, Chatzifrangkeskou M, Rodriguez B et al. (2018) Rescue of biosynthesis of nicotinamide adenine dinucleotide protects the heart in cardiomyopathy caused by lamin A/C gene mutation. Human Molecular Genetics 27:3870-3880. PMID: https://pubmed.ncbi.nlm.nih.gov/30053027/

27. Bonora M, Patergnani S, Rimessi A et al. (2012) ATP synthesis and storage. Purinergic Signalling 8:343-357. PMID: https://pubmed.ncbi.nlm.nih.gov/22528680/

28. Lopez-Otin C, Blasco M, Partridge L et al. (2013) The hallmarks of aging. Cell 153:1194-1217. PMID: https://pubmed.ncbi.nlm.nih.gov/23746838/

29. Fang E, Lautrup S, Hou Y et al. (2017) NAD+ in aging: molecular mechanisms and translational implications. Trends in Molecular Medicine 23:899-916. PMID: https://pubmed.ncbi.nlm.nih.gov/28899755/

30. Imai S, Guarente L (2014) NAD+ and sirtuins in aging and disease. Trends in Cell Biology 24:464-471. PMID: https://pubmed.ncbi.nlm.nih.gov/24786309/

31. Yoshino J, Baur J, Imai S (2018) NAD+ intermediates: the biology and therapeutic potential of NMN and NR. Cell Metabolism 27:513-528. PMID: https://pubmed.ncbi.nlm.nih.gov/29249689/

32. Mouchiroud L, Houtkooper R, Moullan N et al. (2013) The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 154:430-441. PMID: https://pubmed.ncbi.nlm.nih.gov/23870130/

33. Sohal R, Arnold L, Orr W (1990) Effect of age on superoxide dismutase, catalase, glutathione reductase, inorganic peroxides, TBA-reactive material, GSH/GSSG, NADPH/NADP+ and NADH/NAD+ in Drosophila melanogaster. Mechanisms of Ageing and Development 56:223-235. PMID: https://pubmed.ncbi.nlm.nih.gov/2128525/

34. Verdin E (2015) NAD+ in aging, metabolism, and neurodegeneration. Science 350:1208-1213. PMID: https://pubmed.ncbi.nlm.nih.gov/26785480/

35. Altschul R, Hoffer A, Stephen J (1955) Influence of nicotinic acid on serum cholesterol in man. Archives of Biochemistry and Biophysics 54:558-559. PMID: https://pubmed.ncbi.nlm.nih.gov/14350806/

36. Parsons Jr W, Achor R, Berge K et al. (1956) Changes in concentration of blood lipids following prolonged administration of large doses of nicotinic acid to persons with hypercholesterolemia: preliminary observations. Proceedings of the Staff Meetings. Mayo Clinic 31:377-390. PMID: https://pubmed.ncbi.nlm.nih.gov/13336128/

37. Parsons Jr W (2000) Introduction of niacin as the first successful treatment for cholesterol control, a reminiscence. Journal of Orthomolecular Medicine 15:121-126. http://orthomolecular.org/library/jom/2000/pdf/2000-v15n03-p121.pdf

38. Ganji S, Kamanna V, Kashyap M (2003) Niacin and cholesterol: role in cardiovascular disease (review). The Journal of Nutritional Biochemistry 14:298-305. PMID: https://pubmed.ncbi.nlm.nih.gov/12873710/

39. Huber R, Wong A (2020) Nicotinamide: an update and review of safety & differences from niacin. Skin Therapy Letter 25:7-11. PMID: https://pubmed.ncbi.nlm.nih.gov/33196157/

40. Parsons Jr W (2003) Cholesterol Control without Diet! The Niacin Solution. 2nd ed., Scottsdale, AZ: Lilac Press

41. Filler K, Lyon D, Bennett J et al. (2014) Association of mitochondrial dysfunction and fatigue: a review of the literature. BBA Clinical 1:12-23. PMID: https://pubmed.ncbi.nlm.nih.gov/25147756/

42. Pirinen E, Auranen M, Khan N et al. (2020) Niacin cures systemic NAD+ deficiency and improves muscle performance in adult-onset mitochondrial myopathy. Cell Metabolism 31:1078-1090. PMID: https://pubmed.ncbi.nlm.nih.gov/32386566/

43. Schwemmlein J, Maack C, Bertero E (2022) Mitochondria as therapeutic targets in heart failure. Current Heart Failure Reports 19:27-37. PMID: https://pubmed.ncbi.nlm.nih.gov/35147851/

44. Starling R, Hammer D, Altschuld (1998) Human myocardial ATP content and in vivo contractile function. Molecular and Cellular Biochemistry 180:171-177. PMID: https://pubmed.ncbi.nlm.nih.gov/9546644/

45. Tannous C, Booz G, Altara R et al. (2021) Nicotinamide adenine dinucleotide: biosynthesis, consumption and therapeutic role in cardiac diseases. Acta Physiologica 231:e13551. PMID: https://pubmed.ncbi.nlm.nih.gov/32853469/

46. Kalsi K, Smolenski R, Pritchard R et al. (1999) Energetics and function of the failing human heart with dilated or hypertrophic cardiomyopathy. European Journal of Clinical Investigation 29:469-477. PMID: https://pubmed.ncbi.nlm.nih.gov/10354207/

47. Diguet N, Trammell S, Tannous C et al. (2018) Nicotinamide riboside preserves cardiac function in a mouse model of dilated cardiomyopathy. Circulation 137:2256-2273. PMID: https://pubmed.ncbi.nlm.nih.gov/29217642/

48. Abdellatif M, Sedej S, Kroemer G (2021) NAD+ metabolism in cardiac health, aging, and disease. Circulation 144:1795-1817. PMID: https://pubmed.ncbi.nlm.nih.gov/34843394/

49. Trueblood N, Ramasamy R, Wang L, Schaefer S (2000) Niacin protects the isolated heart from ischemia-reperfusion injury. American Journal of Physiology. Heart and Circulatory Physiology 279:H764-H771. PMID: https://pubmed.ncbi.nlm.nih.gov/10924076/

50. Abdellatif M, Trummer-Herbst V, Koser F et al. (2021) Nicotinamide for the treatment of heart failure with preserved ejection fraction. Science Translational Medicine 13:eabd7064. PMID: https://pubmed.ncbi.nlm.nih.gov/33568522/

51. Bays H, Rader D (2009) Does nicotinic acid (niacin) lower blood pressure? International Journal of Clinical Practice 63:151-159. PMID: https://pubmed.ncbi.nlm.nih.gov/19054161/

52. Zhu X, Li J, Wang H et al. (2023) Nicotinamide restores tissue NAD+ and improves survival in rodent models of cardiac arrest. PLoS One 18:e0291598. PMID: https://pubmed.ncbi.nlm.nih.gov/37713442/

53. Airhart S, Shireman L, Risler L et al. (2017) An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers. PLoS One 12:e0186459. PMID: https://pubmed.ncbi.nlm.nih.gov/29211728/

54. Hootkooper R, Canto C, Wanders R, Auwerx J (2010) The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocrine Reviews 31:194-223. PMID: https://pubmed.ncbi.nlm.nih.gov/20007326/

55. Canto C, Menzies K, Auwerx J (2015) NAD(+) metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell Metabolism 22:31-53. PMID: https://pubmed.ncbi.nlm.nih.gov/26118927/

56. Jacobson M, Jacobson E (2018) Vitamin B3 in health and disease: toward the second century of discovery. Methods in Molecular Biology 1813:3-8. PMID: https://pubmed.ncbi.nlm.nih.gov/30097857/

57. Rotllan N, Camacho M, Tondo M et al. (2018) Therapeutic potential of emerging NAD+-increasing strategies for cardiovascular diseases. Antioxidants 10:1939. PMID: https://pubmed.ncbi.nlm.nih.gov/34943043/

58. Mehmel M, Jovanovic N, Spitz U (2020) Nicotinamide riboside-the current state of research and therapeutic uses. Nutrients 12:1616. PMID: https://pubmed.ncbi.nlm.nih.gov/32486488/

59. Sharma C, Donu D, Cen Y (2022) Emerging role of nicotinamide riboside in health and diseases. Nutrients 14:3889. PMID: https://pubmed.ncbi.nlm.nih.gov/36235542/

60. Hong G, Zheng D, Zhang L et al. (2018) Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis. Free Radical Biology & Medicine 123:125-137. PMID: https://pubmed.ncbi.nlm.nih.gov/29803807/

61. Poljsak B, Kovac V, Dahmane R et al. (2019) Cancer etiology: a metabolic disease originating from life's major evolutionary transition? Oxidative Medicine and Cellular Longevity 2019:7831952. PMID: https://pubmed.ncbi.nlm.nih.gov/31687086/

62. Shah G, Shah R, Veillette H et al. (2005) Biochemical assessment of niacin deficiency among carcinoid cancer patients. The American Journal of Gastroenterology 100:2307-2314. PMID: https://pubmed.ncbi.nlm.nih.gov/16181385/

63. Kirkland J (2003) Niacin and carcinogenesis. Nutrition and Cancer 46:110-118. PMID: https://pubmed.ncbi.nlm.nih.gov/14690785/

64. Chen A, Martin A, Choy B et al. (2015) A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. The New England Journal of Medicine 373:1618-1626. PMID: https://pubmed.ncbi.nlm.nih.gov/26488693/

65. Benavente C, Jacobson M, Jacobson E (2009) NAD in skin: therapeutic approaches for niacin. Current Pharmaceutical Design 15:29-38. PMID: https://pubmed.ncbi.nlm.nih.gov/19149600/

66. Canner P, Berge K, Wenger N et al. (1986) Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. Journal of the American College of Cardiology 8:1245-1255. PMID: https://pubmed.ncbi.nlm.nih.gov/3782631/

67. Liu W, Cao S, Shi D et al. (2023) Association between dietary vitamin intake and mortality in US adults with diabetes: a prospective cohort study. Diabetes/Metabolism Research and Reviews Sep 26. Online ahead of print. PMID: https://pubmed.ncbi.nlm.nih.gov/37750562/

68. Langsjoen P, Folkers K, Lyson et al. (1990) Pronounced increase in survival of patients with cardiomyopathy when treated with coenzyme Q10 and conventional therapy. International Journal of Tissue Reactions 12:163-168. PMID: https://pubmed.ncbi.nlm.nih.gov/2276894/

69. Langsjoen P, Langsjoen A (2008) Supplemental ubiquinol in patients with advanced congestive heart failure. Biofactors 32:119-128. PMID: https://pubmed.ncbi.nlm.nih.gov/19096107/

70. Oleck S, Ventura H (2016) Coenzyme Q10 and utility in heart failure: just another supplement? Current Heart Failure Reports 13:190-195. PMID: https://pubmed.ncbi.nlm.nih.gov/27333901/

71. Lei L, Liu Y (2017) Efficacy of coenzyme Q10 in patients with cardiac failure: a meta-analysis of clinical trials. BMC Cardiovascular Disorders 17:196. PMID: https://pubmed.ncbi.nlm.nih.gov/28738783/

72. Langsjoen P, Langsjoen A, Folkers K (1990) A six-year clinical study of therapy of cardiomyopathy with coenzyme Q10. International Journal of Tissue Reactions 12:169-171. PMID: https://pubmed.ncbi.nlm.nih.gov/2276895/

73. Mortensen S, Rosenfeldt F, Kumar A et al. (2014) The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC. Heart Failure 2:641-649. PMID: https://pubmed.ncbi.nlm.nih.gov/25282031/

74. Fotino A, Thompson-Paul A, Bazzano L (2013) Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis. The American Journal of Clinical Nutrition 97:268-275. PMID: https://pubmed.ncbi.nlm.nih.gov/23221577/

75. Langsjoen P, Langsjoen A, Willis R, Folkers K (1997) Treatment of hypertrophic cardiomyopathy with coenzyme Q10. Molecular Aspects of Medicine 18 Suppl:S145-S151. PMID: https://pubmed.ncbi.nlm.nih.gov/9266516/

76. Sobirin M. Herry Y, Sofia S et al. (2019) Effects of coenzyme Q10 supplementation on diastolic function in patients with heart failure with preserved ejection fraction. Drug Discoveries & Therapeutics 13:38-46. PMID: https://pubmed.ncbi.nlm.nih.gov/30880321/

77. Yan H, Zou T, Tuo Q et al. (2021) Ferroptosis: mechanisms and links with diseases. Signal Transduction and Targeted Therapy 6:49. PMID: https://pubmed.ncbi.nlm.nih.gov/33536413/

78. Walker M, Tian R (2018) Raising NAD in heart failure: time to translate? Circulation 137:2274-2277. PMID: https://pubmed.ncbi.nlm.nih.gov/29784680/

79. Griffin S, Pickard M, Orme R et al. (2013) Nicotinamide promotes neuronal differentiation of mouse embryonic stem cells in vitro. Neuroreport 24:1041-1046. PMID: https://pubmed.ncbi.nlm.nih.gov/24257250/

80. Griffin S, Pickard M, Orme R et al. (2017) Nicotinamide alone accelerates the conversion of mouse embryonic stem cells into mature neuronal populations. PLoS One 12:e0183358. PMID: https://pubmed.ncbi.nlm.nih.gov/28817722/

81. Gasperi V, Sibilano M, Savini I, Catani M (2019) Niacin in the central nervous system: an update of biological aspects and clinical applications. International Journal of Molecular Sciences 20:974. PMID: https://pubmed.ncbi.nlm.nih.gov/30813414/

82. Spector R (1987) Niacinamide transport through the blood-brain barrier. Neurochemical Research 12:27-31. PMID: https://pubmed.ncbi.nlm.nih.gov/2952896/

83. Ito T, Sato T, Takanashi Y et al. (2021) A single oral supplementation of nicotinamide within the daily tolerable upper level increases blood NAD+ levels in healthy subjects. Translational Medicine of Aging 5:43-51. https://www.sciencedirect.com/science/article/pii/S2468501121000055

84. Cui X, Chopp M, Zacharek A et al. (2010) Niacin treatment of stroke increases synaptic plasticity and axon growth in rats. Stroke 20671245 https://pubmed.ncbi.nlm.nih.gov/20671245/

85. Shehadah A, Chen J, Zacharek A et al. (2010) Niaspan treatment induces neuroprotection after stroke. Neurobiology of Disease 40:277-283. PMID: https://pubmed.ncbi.nlm.nih.gov/20554037/

86. Maiese K, Chong Z (2003) Nicotinamide: necessary nutrient emerges as a novel cytoprotectant for the brain. Trends in Pharmacological Sciences 24:228-232. PMID: https://pubmed.ncbi.nlm.nih.gov/12767721/

87. Mokudai T, Ayoub I, Sakakibara Y et al. (2000) Delayed treatment with nicotinamide (vitamin B3) improves neurological outcome and reduces infarct volume after transient focal cerebral ischemia in Wistar rats. Stroke 31:1679-1685. PMID: https://pubmed.ncbi.nlm.nih.gov/10884473/

88. Suchard M, Savulescu D (2022) Nicotinamide pathways as the root cause of sepsis-an evolutionary perspective on macrophage energetic shifts. The FEBS Journal 289:955-964. PMID: https://pubmed.ncbi.nlm.nih.gov/33686748/

89. Kujundzic R (2022) COVID-19: are we facing secondary pellagra which cannot simply be cured by vitamin B3? International Journal of Molecular Sciences 23:4309. PMID: https://pubmed.ncbi.nlm.nih.gov/35457123/

90. Altay O, Arif M, Li X et al. (2021) Combined metabolic activators accelerates recovery in mild-to-moderate COVID-19. Advanced Sciences 8:e2101222. PMID: https://pubmed.ncbi.nlm.nih.gov/34180141/

91. Badawy A (2020) Immunotherapy of COVID-19 with poly (ADP-ribose) polymerase inhibitors: starting with nicotinamide. Bioscience Reports 40:BSR20202856. PMID: https://pubmed.ncbi.nlm.nih.gov/33063092/

92. Raines N, Ganatra S, Nissaisorakarn P et al. (2020) Niacinamide may be associated with improved outcomes in COVID-19-related acute kidney injury: an observational study. Kidney360 2:33-41. PMID: https://pubmed.ncbi.nlm.nih.gov/35368823/

93. Kumakura S, Sato E, Sekimoto A et al. (2021) Nicotinamide attenuates the progression of renal failure in a mouse model of adenine-induced chronic kidney disease. Toxins 13:50. PMID: https://pubmed.ncbi.nlm.nih.gov/33440677/

94. Brown O, Heitkamp M, Song C (1981) Niacin reduces paraquat toxicity in rats. Science 212:1510-1512. PMID: https://pubmed.ncbi.nlm.nih.gov/7233236/

95. Hoffer A (1975) Nutrition and schizophrenia. Canadian Family Physician 21:78-82. PMID: https://pubmed.ncbi.nlm.nih.gov/20469184/

96. Morris M, Schneider J, Tangney C (2006) Thoughts on B-vitamins and dementia. Journal of Alzheimer's Disease 9:429-433. PMID: https://pubmed.ncbi.nlm.nih.gov/16917152/

97. Rivadeneira A, Moyer P, Salciccioli J (2019) Pellagra in the USA: unusual manifestations of a rare entity. BMJ Case Reports 12:e230972. PMID: https://pubmed.ncbi.nlm.nih.gov/31570356/

98. Morris M, Evans D, Bienias J et al. (2004) Dietary niacin and the risk of incident Alzheimer's disease and of cognitive decline. Journal of Neurology, Neurosurgery, and Psychiatry 75:1093-1099. PMID: https://pubmed.ncbi.nlm.nih.gov/15258207/

99. Wakade C, Chong R, Bradley E et al. (2014) Upregulation of GPR109A in Parkinson's disease. PLoS One 9:e109818. PMID: https://pubmed.ncbi.nlm.nih.gov/25329911/

100. Hellenbrand W, Boeing H, Robra B et al. (1996) Diet and Parkinson's disease. II. A possible role for the past intake of specific nutrients. Results from a self-administered food-frequency questionnaire in a case-control study. Neurology 47:644-650. PMID: https://pubmed.ncbi.nlm.nih.gov/8797457/

101. Fall P, Fredrikson M, Axelson O, Granerus A (1999) Nutritional and occupational factors influencing the risk of Parkinson's disease: a case-control study in southeastern Sweden. Movement Disorders 14:28-37. PMID: https://pubmed.ncbi.nlm.nih.gov/9918341/

102. Hoffer L (2008) Vitamin therapy in schizophrenia. The Israel Journal of Psychiatry and Related Sciences 45:3-10. PMID: https://pubmed.ncbi.nlm.nih.gov/18587164/

103. Pasternak O, Kubicki M, Shenton M (2016) In vivo imaging of neuroinflammation in schizophrenia. Schizophrenia Research 173:200-212. PMID: https://pubmed.ncbi.nlm.nih.gov/26048294/

104. Ansari Z, Pawar S, Seetharaman R (2022) Neuroinflammation and oxidative stress in schizophrenia: are these opportunities for repurposing? Postgraduate Medicine 134:187-199. PMID: https://pubmed.ncbi.nlm.nih.gov/34766870/

105. Meyer U (2013) Developmental neuroinflammation and schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry 42:20-34. PMID: https://pubmed.ncbi.nlm.nih.gov/22122877/

106. Karlsson H, Dalman C (2020) Epidemiological studies of prenatal and childhood infection and schizophrenia. Current Topics in Behavioral Neurosciences 44:35-47. PMID: https://pubmed.ncbi.nlm.nih.gov/30852763/

107. Rund B (2018) The research evidence for schizophrenia as a neurodevelopmental disorder. Scandinavian Journal of Psychology 59:49-58. PMID: https://pubmed.ncbi.nlm.nih.gov/29356007/

108. Falkai P, Schmitt A (2022) Failed regeneration and inflammation in schizophrenia: two sides of the same coin? Journal of Neural Transmission 129:611-615. PMID: https://pubmed.ncbi.nlm.nih.gov/35451657/

109. Shah D, Pandey S, Rathi R (1972) Psychiatric manifestations in pellagra. The Journal of the Association of Physicians of India 20:575-578. PMID: https://pubmed.ncbi.nlm.nih.gov/4680826/

110. Periyasamy S, John S, Padmavati R et al. (2019) Association of schizophrenia risk with disordered niacin metabolism in an Indian genome-wide association study. JAMA Psychiatry 76:1026-1034. PMID: https://pubmed.ncbi.nlm.nih.gov/31268507/

111. Prakash R, Gandotra S, Singh L et al. (2008) Rapid resolution of delusional parasitosis in pellagra with niacin augmentation therapy. General Hospital Psychiatry 30:581-584. PMID: https://pubmed.ncbi.nlm.nih.gov/19061687/

112. Mahler M, Cummings J, Benson D (1987) Treatable dementias. The Western Journal of Medicine 146:705-712. PMID: https://pubmed.ncbi.nlm.nih.gov/3617715/

113. Xu X, Jiang G (2015) Niacin-respondent subset of schizophrenia-a therapeutic review. European Review for Medical and Pharmacological Sciences 19:988-997. PMID: https://pubmed.ncbi.nlm.nih.gov/25855923/

114. Torrey E, Yolken R (2003) Toxoplasma gondii and schizophrenia. Emerging Infectious Diseases 9:1375-1380. PMID: https://pubmed.ncbi.nlm.nih.gov/14725265/

115. Rantala M, Luoto S, Borraz-Leon J, Krams I (2022) Schizophrenia: the new etiological synthesis. Neuroscience and Biobehavioral Reviews 142:104894. PMID: https://pubmed.ncbi.nlm.nih.gov/36181926/

116. Miklossy J, Khalili K, Gern L et al. (2004) Borrelia burgdorferi persists in the brain in chronic Lyme neuroborreliosis and may be associated with Alzheimer's disease. Journal of Alzheimer's Disease 6:673-681. PMID: https://pubmed.ncbi.nlm.nih.gov/15665404/

117. Sasmita A (2019) Modification of the gut microbiome to combat neurodegeneration. Reviews in the Neurosciences 30:795-805. PMID: https://pubmed.ncbi.nlm.nih.gov/31095511/

118. Wozniak M, Mee A, Itzhaki R (2009) Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques. The Journal of Pathology 217:131-138. PMID: https://pubmed.ncbi.nlm.nih.gov/18973185/

119. Alonso R, Pisa D, Marina A et al. (2014) Fungal infection in patients with Alzheimer's disease. Journal of Alzheimer's Disease 41:301-311. PMID: https://pubmed.ncbi.nlm.nih.gov/24614898/

120. Dominy S, Lynch C, Ermini F et al. (2019) Porphyromonas gingivalis in Alzheimer's disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Science Advances 5:eaau3333. PMID: https://pubmed.ncbi.nlm.nih.gov/30746447/

121. Balin B, Gerard H, Arking E et al. (1998) Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain. Medical Microbiology and Immunology 187:23-42. PMID: https://pubmed.ncbi.nlm.nih.gov/9749980/

122. Jiang C, Li G, Huang P et al. (2017) The gut microbiota and Alzheimer's disease. Journal of Alzheimer's Disease 58:1-15. PMID: https://pubmed.ncbi.nlm.nih.gov/28372330/

123. Fang X (2016) Potential role of gut microbiota and tissue barriers in Parkinson's disease and amyotrophic lateral sclerosis. The International Journal of Neuroscience 126:771-776. PMID: https://pubmed.ncbi.nlm.nih.gov/26381230/

124. Ning J, Huang S, Chen S et al. (2022) Investigating casual associations among gut microbiota, metabolites, and neurodegenerative diseases: a Mendelian randomization study. Journal of Alzheimer's Disease 87:211-222. PMID: https://pubmed.ncbi.nlm.nih.gov/35275534/

125. Zhuang Z, Yang R, Wang W et al. (2020) Associations between gut microbiota and Alzheimer's disease, major depressive disorder, and schizophrenia. Journal of Neuroinflammation 17:288. PMID: https://pubmed.ncbi.nlm.nih.gov/33008395/

126. Picchioni M, Murray R (2007) Schizophrenia. BMJ 335:91-95. PMID: https://pubmed.ncbi.nlm.nih.gov/17626963/

127. Madsen A, Keidling N, Karle A et al. (1998) Neuroleptics in progressive structural brain abnormalities in psychiatric illness. Lancet 352:784-785. PMID: https://pubmed.ncbi.nlm.nih.gov/9737286/

128. Cahn W, Pol H, Lems E et al. (2002) Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Archives of General Psychiatry 59:1002-1010. PMID: https://pubmed.ncbi.nlm.nih.gov/12418933/

129. Emsley R, Asmal L, du Plessis S et al. (2017) Brain volume changes over the first year of treatment in schizophrenia: relationships to antipsychotic treatment. Psychological Medicine 47:2187-2196. PMID: https://pubmed.ncbi.nlm.nih.gov/28347393/

130. Hirayasu Y (2007) Brain imaging in schizophrenia. Neuropathology 27:601-603. PMID: https://pubmed.ncbi.nlm.nih.gov/18021383/

131. Muller N (2018) Inflammation in schizophrenia: pathogenetic aspects and therapeutic considerations. Schizophrenia Bulletin 44:973-982. PMID: https://pubmed.ncbi.nlm.nih.gov/29648618/

132. Marques T, Ashok A, Pillinger T et al. (2019) Neuroinflammation in schizophrenia: meta-analysis of in vivo microglial imaging studies. Psychological Medicine 49:2186-2196. PMID: https://pubmed.ncbi.nlm.nih.gov/30355368/

133. Leng F, Edison P (2021) Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nature Reviews Neurology 17:157-172. PMID: https://pubmed.ncbi.nlm.nih.gov/33318676/

134. Na K, Jung H, Kim Y (2014) The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry 48:277-286. PMID: https://pubmed.ncbi.nlm.nih.gov/23123365/

135. Buckley P (2019) Neuroinflammation and schizophrenia. Current Psychiatry Reports 21:72. PMID: https://pubmed.ncbi.nlm.nih.gov/31267432/

136. Murphy C, Walker A, Weickert C (2021) Neuroinflammation in schizophrenia: the role of nuclear factor kappa B. Translational Psychiatry 11:528. PMID: https://pubmed.ncbi.nlm.nih.gov/34650030

137. Bechter (2013) [Schizophrenia-a mild encephalitis?] Article in German. Fortschritte der Neurologie-Psychiatrie 81:250-259. PMID: https://pubmed.ncbi.nlm.nih.gov/23629631/

138. Osmond H, Hoffer A (1959) A small research in schizophrenia. Canadian Medical Association Journal 80:91-94. PMID: https://pubmed.ncbi.nlm.nih.gov/13618799/

139. Lahteenvuo M, Tiihonen J (2021) Antipsychotic polypharmacy for the management of schizophrenia: evidence and recommendations. Drugs 81:1273-1284. PMID: https://pubmed.ncbi.nlm.nih.gov/34196945/

140. Weller M (1987) The spectrum of schizophrenia. Postgraduate Medical Journal 63:1021-1024. PMID: https://pubmed.ncbi.nlm.nih.gov/3330234/

141. Hoffer A, Osmond H, Callbeck M, Kahan I (1957) Treatment of schizophrenia with nicotinic acid and nicotinamide. Journal of Clinical and Experimental Psychopathology 18:131-158. PMID: https://pubmed.ncbi.nlm.nih.gov/13439009/

142. Sandyk R, Kanofsky J (1993) Vitamin C in the treatment of schizophrenia. The International Journal of Neuroscience 68:67-71. PMID: https://pubmed.ncbi.nlm.nih.gov/8063516/

143. Hoffer A, Prousky J (2008) The proper treatment of schizophrenia requires optimal daily doses of vitamin B3. Journal of Orthomolecular Medicine 23:191-195. http://orthomolecular.org/library/jom/2008/pdf/2008-v23n04-p191.pdf

144. Hoffer A, Prousky J (2008) Successful treatment of schizophrenia requires optimal daily doses of vitamin B3. Alternative Medicine Review 13:287-291. PMID: https://pubmed.ncbi.nlm.nih.gov/19238764/

145. Hoffer A (1994) Chronic schizophrenic patients treated ten years or more. Journal of Orthomolecular Medicine 9:7-37.

146. Hoffer A, Osmond H (1964) Treatment of schizophrenia with nicotinic acid. A ten year follow-up. Acta Psychiatrica Scandinavica 40:171-189. PMID: https://pubmed.ncbi.nlm.nih.gov/14235254/

147. Hoffer A (1963) Nicotinic acid: an adjunct in the treatment of schizophrenia. The American Journal of Psychiatry 120:171-173. PMID: https://pubmed.ncbi.nlm.nih.gov/13963912/

148. Osmond H, Hoffer A (1962) Massive niacin treatment in schizophrenia: review of a nine-year study. Lancet 1:316-319. PMID: https://pubmed.ncbi.nlm.nih.gov/14482545/

149. Hoffer A, Saul A, Foster H (2023) Niacin: The Real Story. Nashville, TN: Basic Health Publications, Inc.

150. Hoffer A (2020) Light on Schizophrenia: Revealing causes and solutions from an orthomolecular perspective. Victoria, BC: Tellwell Publishing

151. Hoffer A (1971) Megavitamin B-3 therapy for schizophrenia. Canadian Psychiatric Association Journal 16:499-504. PMID: https://pubmed.ncbi.nlm.nih.gov/4947171/

152. Hoffer A (1973) A neurological form of schizophrenia. Canadian Medical Association Journal 108:186. PMID: https://pubmed.ncbi.nlm.nih.gov/4684627/

153. Premkumar V, Yuvaraj S, Vijayasarathy K et al. (2007) Effect of coenzyme Q10, riboflavin and niacin on serum CEA and CA 15-3 levels in breast cancer patients undergoing tamoxifen therapy. Biological & Pharmaceutical Bulletin 30:367-370. PMID: https://pubmed.ncbi.nlm.nih.gov/17268082/

154. Yuvaraj S, Premkumar V, Vijayasarathy K et al. (2008) Augmented antioxidant status in tamoxifen treated postmenopausal women with breast cancer on co-administration with coenzyme Q10, niacin and riboflavin. Cancer Chemotherapy and Pharmacology 61:933-941. PMID: https://pubmed.ncbi.nlm.nih.gov/17668211/

155. Premkumar V, Yuvaraj S, Sathish S et al. (2008) Anti-angiogenic potential of Coenzyme Q10, riboflavin and niacin in breast cancer patients undergoing tamoxifen therapy. Vascular Pharmacology 48:191-201. PMID: https://pubmed.ncbi.nlm.nih.gov/18407793/

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Editorial Review Board:

Albert G. B. Amoa, MB.Ch.B, Ph.D. (Ghana)
Seth Ayettey, M.B., Ch.B., Ph.D. (Ghana)
Ilyès Baghli, M.D. (Algeria)
Barry Breger, M.D. (Canada)
Ian Brighthope, MBBS, FACNEM (Australia)
Gilbert Henri Crussol, D.M.D. (Spain)
Carolyn Dean, M.D., N.D. (USA)
Ian Dettman, Ph.D. (Australia)
Susan R. Downs, M.D., M.P.H. (USA)
Ron Ehrlich, B.D.S. (Australia)
Hugo Galindo, M.D. (Colombia)
Gary S. Goldman, Ph.D. (USA)
William B. Grant, Ph.D. (USA)
Claus Hancke, MD, FACAM (Denmark)
Patrick Holford, BSc (United Kingdom)
Ron Hunninghake, M.D. (USA)
Bo H. Jonsson, M.D., Ph.D. (Sweden)
Dwight Kalita, Ph.D. (USA)
Felix I. D. Konotey-Ahulu, M.D., FRCP (Ghana)
Peter H. Lauda, M.D. (Austria)
Fabrice Leu, N.D., (Switzerland)
Alan Lien, Ph.D. (Taiwan)
Homer Lim, M.D. (Philippines)
Stuart Lindsey, Pharm.D. (USA)
Pedro Gonzalez Lombana, M.D., Ph.D. (Colombia)
Victor A. Marcial-Vega, M.D. (Puerto Rico)
Juan Manuel Martinez, M.D. (Colombia)
Mignonne Mary, M.D. (USA)
Joseph Mercola, D.O. (USA)
Jorge R. Miranda-Massari, Pharm.D. (Puerto Rico)
Karin Munsterhjelm-Ahumada, M.D. (Finland)
Sarah Myhill, MB, BS (United Kingdom)
Tahar Naili, M.D. (Algeria)
Zhiyong Peng, M.D. (China)
Isabella Akyinbah Quakyi, Ph.D. (Ghana)
Selvam Rengasamy, MBBS, FRCOG (Malaysia)
Jeffrey A. Ruterbusch, D.O. (USA)
Gert E. Schuitemaker, Ph.D. (Netherlands)
Thomas N. Seyfried, Ph.D. (USA)
Han Ping Shi, M.D., Ph.D. (China)
T.E. Gabriel Stewart, M.B.B.CH. (Ireland)
Jagan Nathan Vamanan, M.D. (India)

Andrew W. Saul, Ph.D. (USA), Editor-In-Chief
Associate Editor: Robert G. Smith, Ph.D. (USA)
Editor, Japanese Edition: Atsuo Yanagisawa, M.D., Ph.D. (Japan)
Editor, Chinese Edition: Richard Cheng, M.D., Ph.D. (USA)
Editor, Norwegian Edition: Dag Viljen Poleszynski, Ph.D. (Norway)
Editor, Arabic Edition: Moustafa Kamel, R.Ph, P.G.C.M (Egypt)
Editor, Korean Edition: Hyoungjoo Shin, M.D. (South Korea)
Editor, Spanish Edition: Sonia Rita Rial, PhD (Argentina)
Editor, German Edition: Bernhard Welker, M.D. (Germany)
Associate Editor, German Edition: Gerhard Dachtler, M.Eng. (Germany)
Assistant Editor: Michael Passwater (USA)
Contributing Editor: Thomas E. Levy, M.D., J.D. (USA)
Contributing Editor: Damien Downing, M.B.B.S., M.R.S.B. (United Kingdom)
Contributing Editor: W. Todd Penberthy, Ph.D. (USA)
Contributing Editor: Ken Walker, M.D. (Canada)
Contributing Editor: Michael J. Gonzalez, N.M.D., Ph.D. (Puerto Rico)
Technology Editor: Michael S. Stewart, B.Sc.C.S. (USA)
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