Monday, April 10, 2017

Niacin Therapy for Schizophrenia - Pellagra

Niacin Rescues Cannibalistic Hamsters

Posted on: Monday, April 10th 2017 at 7:00 am

Originally published on Orthomolecular.org.

Study finds that hamsters who ate primarily corn-based diets exhibited siblicide and maternal infanticide.  

Orthomolecular Medicine News Service, February 28, 2017
Niacin Rescues Cannibalistic Hamsters
The Historical Significance of 1940s Mandatory Niacin Enrichment
by W. Todd Penberthy, PhD

(OMNS, Feb 28, 2017) In a newly published research study, Tissier and colleagues at the Universite ' de Strasbourg, France, identified wild hamsters that were eating primarily corn monoculture diets and exhibiting siblicide and maternal infanticide. Cannibalism was one of the theories for the decline of their population. Mother hamsters fed exclusively corn would take their pups, place them together with the stashes of corn they had stored in the cage, and start eating their young. Siblicide was also observed. Only 5 percent of the offspring of the females fed corn survived. The rest were eaten. For the other group fed a varied diet, 80 percent of the babies survived. However, supplementation of corn diets with just vitamin B3 (niacin) prevented the aggressive cannibalistic behavior.[1] 
Niacin fortification
This recently published study raises the question of the historical significance of the timing of mandatory niacin fortification starting in 1942.[1,2] Mandatory fortification of the vitamin niacin in the United States was initiated at the precise moment when our society became aware of the need to rebuild. The historical tide began to change from "Let's see how many people we can kill with all these new ways to kill each other" to, "I'm sorry, let's rebuild your country" and ultimately to "I want that Westy/Volkswagen camper!" today. Was niacin fortification an integral to rescuing an otherwise excessively violent world in the 1940s?

The niacin-deficiency disease pellagra became more common after roller mills were used on an industrial scale in the United States starting in the 1880s. Although white flour had been available during the previous century, it was expensive and only available for the wealthy. Roller-milled wheat and corn were now inexpensive, and had a long shelf life. But this industrially processed corn was not correctly treated with alkali as practiced by the ancient Maya and Aztec people. Soon thereafter the masses enjoyed white flour and the new form of processed grits, but then came an epidemic of pellagra! Before the discovery of niacin, over 100,000 people died in the southern United States alone due to pellagra epidemics. Shortly after the discovery of niacin, scientists and medical professionals including Dr. Goldberger and Dr. Abram Hoffer helped to establish mandatory fortification in the 1940s.[3] 

Modern hominy is created by soaking corn in alkali as the ancients did in a process called nixtamalization. This allows niacin and tryptophan, its precursor, to be available for absorption in the gut. Although hominy grits are missing the bran and germ of the kernel that contain much of its vitamin content, they generally supply enough niacin to prevent pellagra in those who eat mainly corn. 

Pellagra symptoms are conveniently remembered by the "4 Ds": diarrhea, dementia, dermatitis, and death. Changes in behavior are difficult to measure, but mortality statistics for the United States suggest that pellagra was perhaps the most severe nutritional deficiency disease ever recorded in US history.[2] With the fortification of niacin in white flour and bread, mortality rates were decreased by orders of magnitude in some states within a couple of years! This underscores the critical sensitivity of all animals including humans to niacin deficiency. 

"Improperly cooked maize-based diets have been associated with higher rates of homicide, suicide and cannibalism in humans," according to Gerard Baumgart, a scientist and expert on European hamsters. Epidemiological studies have confirmed this. [7] 

Pellagra or schizophrenia?
Nearly a decade after the initiation of niacin fortification in the 1940s, Dr. Hoffer noticed similarities between pellagra and the schizophrenic patients he was treating, so he considered that perhaps these individuals needed higher amounts of niacin. In the 1950s and later, Hoffer treated over ten thousand schizophrenics with high doses of niacin. He showed that many schizophrenics can be successfully treated with niacin administered in high doses divided throughout the day. In Hoffer's last book, Psychiatry Yesterday and Today, he said "Schizophrenia is not a multivitamin deficiency disease." It is in fact the disease pellagra; a vitamin B3-dependency disease. It will not be treated successfully no matter how many dozens of vitamin pills are given if these patients are not given the correct doses of this vitamin." [4] Hoffer and other practicing physicians have observed that high doses of niacin can work for the treatment of acute schizophrenia, but it is not as effective for longstanding cases. 

Before niacin was discovered, there was a focus on corn and grits in particular because of their high correlative association with pellagra.[5,6] At the end the 19th century, this intense focus developed into medical conferences organized to discover the cause of pellagra. 
But cannibalism?
On first thought, it seems incredible that a single vitamin can prevent a behavior as complex as cannibalism. How could niacin do this and exert so many other benefits? Niacin is converted to NAD (nicotinamide adenine dinucleotide) in the liver. NAD is involved in more reactions than any other vitamin-derived cofactor; over 400 different reactions (see database: https://www.cmescribe.com/vitamin-dependent-gene-databases/). NAD is required for basic bioenergetics (glycolysis and beta oxidation) and in P450 reactions like the phase I detoxification enzymes. Niacin is depleted by a wide variety of stresses (hyperglycemia, aerobic, ionizing radiation), pollutants, and more. Most practically, people with genetic polymorphisms in the DNA encoding for the NAD binding domain that result in reduced binding affinity for any of these greater than 400 different reactions can require higher amounts of niacin to prevent pathologies.[8] These people are niacin-dependent. Dr. Abram Hoffer observed this condition in many schizophrenic patients. 

History and this study of hamsters suggest that aggressive, unempathetic behavior may be an indication for a need for higher levels of niacin in the diet that could be met by high dose niacin therapy. With so many psychologically disturbed acts of violence occurring after years of trying to save individuals with pharmaceuticals, it may seem ironic that high doses of niacin have not been generally employed to help these individuals to more clearly sense the beauty of life. 
How niacin is used as therapy
Dr. Abram Hoffer's approach to niacin therapy involves administration of 1 gram (1,000 mg) taken 3 times a day. This high dose niacin therapy has an exceptional safety profile. It has been used for over 60 years and is lacking serious adverse events, except for when using the slow release types, which can cause hepatic toxicity.[9] The common type of plain niacin, inexpensive and available over the counter, is not slow-release. It is considered "immediate release." Therapy with plain niacin (also known as nicotinic acid) is far less expensive than pharmaceutical treatment. 
When taking plain niacin for the first time, it is important to start at low doses because it gives a "niacin flush" on the skin. This is a vitamin that one will notice for sure. So get to know the flush by first taking 100mg of niacin (nicotinic acid form) and then gradually trying higher amounts up to 1000mg at a time until you notice the flush. A little flush is ideal for health. It raises HDL levels more than any pharmaceutical (including statins), lowers triglycerides, lowers VLDL, and has a better safety profile than statins. 
Niacin and eyesight
Cystoid macular edema has been observed, but only in rare instances, when daily niacin doses are over 3 grams (3,000 mg). If during high-dose niacin therapy you experience blurred vision, reduce or stop taking the niacin and see your medical doctor. 

In a recent study, niacin (in the form of niacinamide) was shown to be effective in reducing (by more than 90%) the development of glaucoma in a strain of glaucoma-prone mice.[10] Glaucoma is a leading cause of blindness world-wide. It is thought to be caused by a sequence of pathological events including an increase in pressure inside the eye, which reduces the blood flow into the eye and damages the eye's energy metabolism. When compounded with improperly functioning mitochondria in retinal neurons the result is cell death and blindness.[11] A very high dose of niacinamide was therapeutic, especially in aged mice, and helped damaged mitochondria to support normal metabolism, allowing retinal neurons to survive.[10] 

The concept of orthomolecular medicine was born and pioneered by Dr. Linus Pauling in the 1960s with the inspiration of Dr. Abram Hoffer. Under pathological conditions, our body naturally needs much more than average amounts of certain vital nutrients due to stress-mediated vitamin/mineral depletions. Historically, this first involved administration of high doses of the essential vitamins B3 and C for the treatment of mental health disorders and cancer respectively, but the full list of responsive indications is always expanding and depends on the individual's symptoms. As compared to pharmaceuticals, vitamins are exceptionally safe and have withstood the test of time [http://orthomolecular.org/resources/omns/v13n01.shtml ].
Conclusion
Some niacin researchers believe that many people with mental illness might be saved if more physicians can end their subscription to the mantra "let's develop foreign chemicals and drugs" as medicine and instead consider "maybe some people have subtle genetic differences that make them require higher amounts of niacin." This theory has already been proven for several niacin vitamin-responsive genetic conditions.[8,10] 
Orthomolecular medicine: fix what's broken with your body's flesh and bones, not foreign chemicals. 
(W. Todd Penberthy is a niacin researcher and medical writer. His PhD is in biochemistry from the University of Tennessee. He was previously a professor at the University of Central Florida, and before that at the University of Cincinnati.) 



For evidence-based research on niacin, visit the GreenMedInfo.com Research Dashboard.
References:
1. Tissier ML, Handrich Y, Dallongeville O, Robin JP, Habold C. (2017) Diets derived from maize monoculture cause maternal infanticides in the endangered European hamster due to a vitamin B3 deficiency.  Proc Biol Sci. 2017 Jan 25;284(1847). pii: 20162168. doi: 10.1098/rspb.2016.2168. http://rspb.royalsocietypublishing.org/content/284/1847/20162168 PMID:28100816 https://www.ncbi.nlm.nih.gov/pubmed/28100816
2. Park, Y. K., Sempos, C. T., Barton, C. N., Vanderveen, J. E., & Yetley, E. A. (2000). Effectiveness of food fortification in the United States: the case of pellagra. Am J Public Health, 90(5), 727-738. 
3. Hoffer, A. (2005). Adventures in Psychiatry: The Scientific Memoirs of Dr. Abram Hoffer KOS Publishing. 
4. Hoffer, A. (2009). Psychiatry Yesterday (1950) and Today (2007): From Despair to Hope with Orthomolecular Psychiatry: Trafford Publishing. 
5. Etheridge, E. W. (1972). The Butterfly Caste: A Social History of Pellagra in the South. Westport, Conn: Greenwood Pub Co. 
6. Roe, D.A. (1973). A Plague of Corn: The Social History of Pellagra (Ithaca NY: Cornell University Press). 
7. Mawson, A., & Jacobs, K. (1978). Corn Consumption, Tryptophan, and Cross-National Homicide Rates. Orthomolecular Psychiatry, 7(4), 227-230. 
8. Ames, B. N., Elson-Schwab, I., & Silver, E. A. (2002). High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms. Am J Clin Nutr, 75(4), 616-658. 
9. Guyton, J. R., & Bays, H. E. (2007). Safety considerations with niacin therapy. Am J Cardiol, 99(6A), 22C-31C. 
10. Williams PA, Harder JM, Foxworth NE, Cochran KE, Philip VM, Porciatti V, Smithies O, John SW. (2017) Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice. Science. Feb 17;355(6326):756-760. doi:10.1126/science.aal0092 
11. Smith RG. (2012)The Vitamin Cure for Eye Disease: How to Prevent and Treat Eye Disease Using Nutrition and Vitamin Supplementation.  Basic Health Pub. ISBN-13: 978-1591202929. 
12. Penberthy, W. T. (2013). Niacin, riboflavin, and thiamine. In: M. H. Stipanuk & M. A. Caudill (Eds.), Biochemical, physiological, and molecular aspects of human nutrition (3rd ed, pp.540-564). St. Louis, Mo: Elsevier/Saunders. 





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