The Magic of Niacin

Since the 1950s, Dr Abram Hoffer, MD, PhD, healed countless hearts and minds with his discovery of megadose niacin (vitamin B3) therapy for schizophrenia. This heralded the onset of megavitamin therapy, starting as a niacin/vitamin C treatment. As the therapy developed, other nutrients and health considerations were included, per unique individual requirements.

Eventually niacin and megavitamin treatment contributed to the recovery or great improvement of tens of thousands of people with schizophrenia: voices and psychosis gone, rare, or significantly muted. Niacin may also play a prominent role in bipolar therapy, especially if voices or anxiety are involved.

My earlier blogposts discuss this further: https://www.boragebooks.com/schizophrenia-blog.html

For details and studies, see my books, Natural Healing for Schizophrenia and Natural Healing for Bipolar Disorder at https://www.boragebooks.com/

Edelman podcast interview on Wellness for Life

My recent interview on webmd with Dr Susanne Bennett can be found on her website at
http://radiomd.com/show/wellness-for-life-radio/item/38075-natural-treatments-for-bipolar-disorder
or go to  iTunes at
https://apple.co/2NVJ8bw 
and click on Natural Treatments for Bipolar Disorder

SAMe, happiness and serotonin

What exactly is SAMe?
SAMe is known popularly for its antidepressant effectiveness.
SAMe (S-adenosyl methionine) is derived from the essential amino acid methionine with the help of magnesium and ATP (our energy currency, produced in the mitochondria) and the enzyme MAT.
SAMe is the key methyl donor in the body.
Methylation is critical to body function. It is required in creation of creatine (which recycles ADP into ATP), and proper function of DNA, neurotransmitters, proteins, lipids, and enzymes; also, in creating glutathione (our most important antioxidant) and SAMe, in making serotonin more available, and in removing histamine and excess estrogen.
SAMe is fundamental to redressing undermethylated brain chemistry, which occurs in some 35% of bipolars, and is characterized by chronic severe depression.

Increasing serotonin in the synapse
As pointed out by Dr Walsh, methylation by SAMe or methionine reduces genetic expression of reuptake transporters that ferry serotonin out of  the synapse and back to the initial neuron. Decreased transporters mean that more serotonin accumulates in the synapse. The more the serotonin in the synapse, the more serotonin messages. Optimal serotonin makes us happy and content, and better able to handle stress.

Other Effects
SAMe also works on other consequences of undermethylation, such as:
fatigue, insomnia and low melatonin, oxidative stress, low glutathione
migraine, chronic pain, compulsions, addictions
metal toxicity, immune and liver issues, cirrhosis
low acetylcholine, phospholipids, and taurine
hormone dysregulation, excess estrogen

Intake
In the treatment for most depressed undermethylators (as indicated by high whole blood histamine and/or a low SAMe/SAH ratio), SAMe and/or methionine are introduced gradually until the correct level becomes evident. This is done in the context of the full range of treatments for undermethylation.

Warnings
Methylation is required for major brain and body functions. Thus, corresponding intake of SAMe and/or methionine for the undermethylated individual should support optimal health. However, if starting to feel too good, dosage should be backed down, in some cases stopped, to prevent hypomania or mania.
If already overmethylated (low blood histamine, high SAMe/SAH), and so, overstimulated (and prone to anxiety/panic; perhaps, hyperactivity, hypomania, mania, psychosis, paranoia or aggression), SAMe and methionine are entirely contraindicated (methylation does not need to increase further). SAMe/methionine are also contraindicated if taking SSRIs.

Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Even within the undermethylated (histadelic) subgroup, each person's biochemical requirements tend to be unique. So if you need treatment for depression, mania, bipolar, or any other medical condition, please consult a knowledgeable physician. 

For a wider view of SAMe, undermethylation and bipolar disorder, you may want to see the 2018 edition of my book, Natural Healing for Bipolar Disorder
                available here.

To contact me, click here. Your purchase at BorageBooks.com supports my work.

Announcing the New 2018 Edition of Natural Healing for Bipolar Disorder

Natural Healing for Bipolar Disorder

The 2018 edition of  Natural Healing for Bipolar Disorder is out! Readers can thank Hyla Cass, MD, who impressed on me the need to update the research. So, after numerous interviews and conferences, and after pouring through the past ten years of studies, voila!
This book is a compendium of more than seven decades of scientific work, worldwide, on nutrient and herbal approaches for bipolar disorder. It is geared to both general public and health professional and researcher. It offers physicians an in-depth view of potential treatments, nutrient-relevant symptoms, labs and research. And it gives patients and other interested persons insight into nutrients and health issues relevant to them, and a means to have more effect on treatment choices.

Some of the highlights of the new compendium:

• The latest in bipolar research, including the Walsh/ deVito theory, which suggests difficulty  removing extra-neuronal potassium is a major cause of moodswing.
• Genes are not everything! The book looks at how nutrients like folate, methionine, SAMe, and niacin change the extent to which genes that influence mood are expressed (epigenetics).
• Further refinements on pyroluria (a stress disorder) and methylation therapies, including a methylation diagram which emphasizes nutrients.
• Added emphasis on the effects of folate, the copper/zinc balance, essential fatty acids, and antioxidants. 
• A new, more effective, less damaging, metal detox approach.
• More on allergic/ immune reactions, inflammation, autoimmunity, and cellular energetics.
• Additional info on specific nutrients, diet, sugar metabolism, gut issues, endocrines, other health factors.
• Updated resources, expanded references.

Available here.

Influence of Copper and Metals on Mania, Voices and Paranoia

The influence of copper and metal metabolism on stimulation, mania, voices and paranoia: http://naturalhealingforschizophrenia.blogspot.com/2014/01/iiib-metal-metabolism-copper-paranoia.html
Also see previous posts on histapenia.
To learn more about copper, toxic metals, mania, and bipolar vitamins, get my book, Natural Healing for Bipolar Disorder, from Borage Books, here, and you also get a FREE educational phone consult.

Histapenia (overmethylation low folate)

For info on vitamin approaches  for histapenia (brain overmethylation, low folic acid), a biotype affecting up to 25% of bipolars, especially when more prone to mania or paranoia, see my Natural Healing for Schizophrenia blog at http://naturalhealingforschizophrenia.blogspot.com/
Check posts June 25, 2013 to Sept 19. (More to follow shortly.)
You can find the complete rundown in either of my books, Natural Healing for Bipolar Disorder or Natural Healing for Schizophrenia, available at http://boragebooks.com
Questions? You get a free educational consult when you buy my book at http://boragebooks.com

IV. Bipolar Creativity: Chemistry and Vitamins

Bipolar chemistry may foster creativity.

It may be that the increased brain stimulation in mania (and positive-symptom schizophrenia) helps provide that particular blend of openness, obsession, intensity, and altered perception which fuels creativity (or provides the insights to be expressed during calmer states).

Thus, methylation imbalances, heightened activity of dopamine, norepinephrine, serotonin, histamine, thyroid, pituitary, etc.; and/or increased receptor sensitivity to such biochemicals may contribute not only to mania or psychosis, but also, creativity.

Perhaps all "creatives" have a little bit of bipolar (or schizophrenia) in them.

Perhaps "creatives" not diagnosed with bipolar or schizophrenia also manifest some of the above chemistry, but possess greater balancing mechanisms--better defense against oxidative stress and toxins, more balanced methylation activity, more accurate metal metabolism, more efficient use of calming nutrients; stabler hormone homeostasis, etc. Or, perhaps, just more optimal intake of supportive nutrients.

Why heal?

Are  extreme moods intrinsic to creativity? Possibly, however, family members, people who have similar genetics but not evident bipolar or schizophrenia, can be particularly creative. On the other hand, studies suggest that bipolar I individuals often begin -- but do not complete -- creative endeavors.
Does one need extremes of irritability, paranoia, isolation, recklessness, and confusion to be creative?

What about a healing approach that nourishes the brain, rather than coercing it, an approach that enables the brain to optimize function with needed nutrients... Consider that the late and great Dr. Abram Hoffer, who had worked with over 10,000 patients, has said something to the effect that people who recover with orthomolecular treatment no longer have the adverse symptoms, but just seem to be more creative that everyone else.

To learn more about nutrient-based approaches, see my books, Natural Healing for Bipolar Disorder, and Natural Healing for Schizophrenia, here
Buy at boragebooks.com. and you also get a free educational consult.

Reminder: The information in this blog is presented for educational purposes only, and is not intended for diagnostic or treatment purposes. If you need treatment for mood disorder or any other medical condition, please consult a knowledgeable physician.

III. Bipolar Biotypes and Creativity

Biotype creative tendencies 

Doctors William Walsh, PhD, (2006, 2007) and Carl C Pfeiffer,  (1987, 1988), who have overseen nutrient-based treatment of approximately 20,000 psych patients each, have noted particular types of creativity associated with biotype.

Histapenia. Artistic or musical interest/creativity. (Pfeiffer 87, 88, Walsh 2006)

Histadelia.  Often perfectionist, competitive, compulsively productive and creative, highly accomplished (Pfeiffer); and frequently excels in science, business, and left brain activity. (Walsh)

Pyroluria. Pfeiffer has stated that pyrolurics are among his most original patients and that many great people were pyroluric, despite the mental anguish and physical deterioration caused by the illness.

For descriptions of these biotypes, corresponding nutrients, and relevance to bipolar, see my book, Natural Healing for Bipolar Disorder.
Get a free educational consult (by phone) when you purchase from http://boragebooks.com/orderBooks.html

This is the third in a series on bipolar and creativity.

II. Creativity / Bipolar Intersections

Temperament, cognitive style, and mood, are notably similar in "creative" individuals and bipolars (perhaps, particularly bipolar IIs). The bipolar syndrome, for example,  involves such creative characteristics as manic love of words, sexual seduction via the arts (poetry, music art, food, fashion, etc.), hypersensitivity to others, etc. (Janza 2004, Akiskal 2005, Fieve 1976, Nettle 2002, Kubie 1961)

Creatives often experience such bipolar traits as:

-- Creative surges and blocks similar to mood swings. (Kubie 1961, Fieve 1976)
-- Sudden change of mood immediately preceding creative periods (in perhaps 50%). (Jamison 1989)
-- Affective temperaments. Cylcothymia. (Nowakowska 2005)
-- Tendency to emotional problems and vulnerability. (Fieve 1976)
-- Emotional flooding; confusing, conflicting passions and ideas; unconventional or restless behavior. (Andreason 1987)
-- Overinclusive thinking, rich associations, or hypomania. (Janza 2004)
-- Reduced sleep, or sudden early waking prior to creative episodes. (Jamison 1989)
-- Unique, unconventional, eccentric, erratic perceptions. (Andreason 1987, Fieve 1976)
-- Ornamental, flamboyant (e.g., wearing red and bright colors). (Akiskal 2005)
-- Tolerance for ambiguity. (Rottenberg 2001)
-- Curiosity, risk taking, adventuresome. (Andreason 1987, Rottenberg 2001)
-- Creativity, novelty-seeking (Nowakowska 2005), impulsivity.  (Akiskal 2005)
-- Eminence, creative achievement, professional instability.  (Akiskal 2005)
-- High energy and activity. (Rottenberg 2001)
-- Excess sociability, frequent moving, different jobs. (Andreason 1987, Fieve 1976)
-- Multiple marriages. (Akiskal 2005)
-- Multiple substance abuse, addiction (Andreason, Akiskal 2005)
-- Comorbidity, irritability, anxiety, neuroticism. (Nowakowska 2005)

Taken mostly from my book, Natural Healing for Bipolar Disorder, which see, for extensive info on nutrients, herbs, allergies, toxicity, and health factors. Get a free educational consult (by phone) when you purchase from http://boragebooks.com/orderBooks.html

This is the second in a series on bipolar and creativity. More in the following posts.

I. Creativity and Bipolar

The link to bipolar

A disproportionate number of bipolars (and families) experience heightened creativity, leadership, or spirituality -- more so than the rest of the population. Similarly, mood disorder is particularly common among individuals classically recognized as creative (Janza 2004) and may help inspire and drive the poet, playwright, or musician. (Fieve 1976)

Some of the research

In an extensive review of historical observations, biographies, scientific surveys, and psychiatric evaluations, Janza (2004) found bipolar symptoms more frequent in the "creative." Moreover, during intense creative expression, artists and writers often report hypomanic symptoms (Janza 2004), and most seem to experience a mood/creativity interaction. (Andreason 1987, Fieve 1976)

In a survey of 47 British writers and artists, Kay Jamison, PhD, (1989) found the greatest prevalence of psychiatric conditions in poets, then writers. Half the poets, two-thirds of the playwrights, 20% of biographers, 13% of painters had been treated for depression. 17% of poets had been treated for mania. All poets, novelists, and artists, 88% of playwrights, and 20% of biographers experienced intense creative episodes characterized by enthusiasm, euphoria, high energy, confidence, fast mental associations, and fluid thought. 63% of playwrights had been treated for mood disorder. 38% of the entire group had received treatment for affective illness (a rate six times that of the general population); one third of the group had severe mood swings; one fourth, intense elated mood states, 50% had taken psychiatric medications, 20% had been previously hospitalized, and 90% reported creative highs lasting an average of two weeks (a typical span for manic elation). (Jamison 1989)

Similarly, Andreason (1987) found substantially greater affective illness, particularly bipolar disorder, among 30 writers (teachers at the University of Iowa creative writing workshop) studied over 15 years. 80% had experienced a mood episode (compared to 30% in controls); 37%, major depression (17%  in controls); 30%, alcoholism (7%, controls). Most wrote during normal mood. First degree relatives also showed greater affective disorder and creativity.

In Arnold M Ludwig's biographical survey of 1005 famous persons in the 20th century, rates of psychosis, suicide attempts, mood disorder, drug and alcohol use were two-to three fold greater in writers and artists than in people successful in business, science or public life. Mania and suicide occurred most in poets. Writers and relatives had very high rates of bipolar psychosis.

Taken mostly from my book, Natural Healing for Bipolar Disorder, which see, for extensive info on nutrients, herbs, allergies, toxicity, and health factors. Get a free educational consult (by phone) when you purchase from http://boragebooks.com

More on bipolar and creativity in the following posts.

Note: Histapenia series beginning

Just to let you know, I am starting a series of posts on histapenia in my schizophrenia blog: http://naturalhealingforschizophrenia.blogspot.com
The introductory post is dated June 25, and is on Dr. Hoffer's seminal work with niacin and C. Subsequent posts will deal directly with histapenia.
Histapenia is found in approximately 25% of bipolars, but up to 50% of schizophrenics -- which is why I have placed it on the schizophrenia blog.

For a compendium of nutrient-based approaches for bipolar disorder, see my book, Natural Healing for Bipolar Disorder.
Available here.
You may also be interested in Natural Healing for Schizophrenia.
Available here.

Bipolar nutrient research: Optimizing design

The interaction of nutrients and herbs with human health is as intricate as nature herself and presents multiple challenges to research design. Here we address ourselves specifically to bipolar research.

Important distinctions in biochemistry need to be controlled for

Effects of nutrients on other biological processes which might confound results.
And conversely, effects of individual biochemistry, epigenetics, and health on how nutrients are used.
Discerning relevant subgroups with distinct biochemical requirements and patterns of response.
Whether to use the entire complex of nutrients which work together toward a specific outcome or somehow control for the effects of using single nutrients isolated from that complex.

Sufficiently long studies

Long enough to assess nutrient benefit. Most nutrients and many herbs do not produce dramatic drug-like effects. But improvement tends to compound over the months and years.
And specificially for bipolar:
Most studies are too short to adequately account for the effects of cycling or shifts in cycling patterns.
Info on long-term effectiveness is critical* since treatments usually must be sustained for life (e.g., decades elapsed before it was realized that overuse of antidepressant drugs could trigger mania, increase cycling and worsen long-term outcome).

Moral considerations when studying bipolar

How morally can the researcher set up sufficiently lengthy controlled blinded studies involving nutrients (which are, by definition, critical to health), when he/she believes it likely that lack of those nutrient in controls could increase bipolar severity, possibly with permanent repercussions.

Additional issues specific to bipolar research

Manic participation may be sporadic, or end abruptly, perhaps leaving only people with milder manias in the study.
People commonly do not report hypomania or mania; and researchers can readily mistake hypomania for signs of health.
Bipolar reactions to minor stressors, even the study, can distort results.

Biases favoring pharmaceuticals

Horrobin (2002) points out that 40-60% of subjects typically drop out of six-to-eight-week studies of psychiatric medications, mostly to avoid side effects. So info on drawbacks is lost, and the data is slanted toward positive outcomes.
Effects of drugs, polypharmacy,  and drug withdrawal are not readily teased out from effects of illness. Medication rebounds, for instance, are often construed as bipolar deterioration (e.g., in many early studies, lithium was withdrawn abruptly in controls, a practice now known to promote mania).
The common protocol of comparing a new medication to one already in use presumes a lack of flaws in the original studies -- a notion often not borne out.
The high cost of large double-blinds skew the body of research away from substances like vitamins, which are unlikely to return enough profit to encourage much funding. Abramson (2004), moreover, finds research financed by drug companies is five times more likely (than if funded more impartially) to uphold the company's drug-of-choice.

The value of open naturalistic, longitudinal studies

So while double blinds (with optimal controls) will always have their place, the complexity of factors involved, and the need long studies, have led a number of bipolar researchers (both mainstream and orthomolecular) to increasingly value open, naturalistic, longitudinal studies. Particularly when backed by periodic biochemical tests (and, as relevant, genetic tests), this type of design particularly lends itself to exploring how bipolars fare, long-term, with multiple nutrients, tailored to health, diet, medication, evolving biochemistry, cycling pattern, etc.

For an extensively-referenced compendium of nutrient-based approaches for bipolar disorder, see my book, Natural Healing for Bipolar Disorder.
Available here.
You may also be interested in Natural Healing for Schizophrenia.
Available here.

This information is presented for educational purposes only, and is not intended for diagnostic or treatment purposes. If you need treatment for mood disorder or any other medical condition, please consult a knowledgeable physician.

Orthomolecular Psychiatry: Hoffer-Pfeiffer-Walsh Outcomes

Scurvy and pellagra (see previous post) are not the only conditions in which severe mental symptoms are "cured" by vitamins.
Others include:
Wernicke-Korsakoff psychosis, associated with B1 depletion due to chronic alcoholism.
The dementia caused by difficulty absorbing and/or insufficient intake of B12.
The depression associated with lack of vitamin D and sunlight.
The depression of iron, copper, or B6- deficiency anemia.
And so on.

The basis of medical treatment: A period of sufficient intake of respective vitamins to resolve the psychosis / dementia / mood symptoms for almost all patients.

So perhaps we can extrapolate the power of nutrients to address those same symptoms in some of what is now thought of as exclusively psychiatric disorders.

Hoffer-Pfeiffer-Walsh Clinical Outcomes

To support this contention, we can look to the clinical outcomes reported by Drs. Hoffer, Pfeiffer and Walsh. Together, these three giants of orthomolecular psychiatry, treated at least 50,000 patients with severe psychiatric disorder, focusing on nutrients tailored to individual biochemical requirements, and considering, where relevant, metal metabolism, environmental toxins, and confounding health conditions. Outcome for schizophrenia, anxiety, and mood disorders was 75-85% great-improvement or recovery, in the higher range when patients were treated early in the illness. Follow-up was generally one year or longer.
Recovery (defined by Hoffer) meant that people could go back to school or work at comparable level to that at which they left off, and that they again got on reasonably well with the people with whom they associate.
Furthermore, each of approximately 40,000 of these patients were assessed with hundreds of tests of nutrients, enzymes, and health status, which correlated nutrient-induced biotype and other biochemical changes with psychiatric improvement.

ABA Subgroup

Which is not to say people get cured, in the sense that to maintain improvement those vitamins tailored to individual biochemical requirements usually must be taken for life. This is actually advantageous because, unlike most meds: nutrient benefits tend to increase slowly but steadily over time; taking many indicated nutrients tends to compound the benefit; and improved physical health is often a side-effect.
Which may have contributed to a decision by many hundreds of the above patients that they were so well they could go off the nutrients. Almost invariably, they deteriorated, then were started again on the vitamins. These situations produced an ABA (on-off-on) within-subject experimental design bolstered by several factors: (1) Most biochemical parameters (except those being manipulated by the vitamins) were as identical as you are going to get (since it was within patient). (2) During the "off" stage, the deterioration was opposite to subject expectations (which was that they were well). (3) Accompanying labs tracked biotype-related biochemistry as it related to psychiatric status.
So this ABA group produced particularly strong data.
The results for almost all patients were deterioration during B, improvement during both A stages, although slower the second time around. Improvement in biotype biochemistry correlated with psychiatric improvement.

How can anyone ignore these amazing outcomes?

Altogether, we have long-term outcome on tens-of-thousands of individuals, reported from three distinct clinics, with most recovering over time, or improving greatly, and with the degree of recovery largely unheard of in mainstream psychiatry. And this, using nutrients, which, by definition, are essential to life, and which, accurately used and tailored to individual requirements, are not going to cause the heart-rending side effects we see with many psych drugs.
Now add to these outcomes the many thousands of positive studies and clinical results from all other nutrient-oriented physicians and researchers, a fertile body of research, constantly expanded by new insights and findings.
And just possibly, what we as a society will find ourselves moving towards is a way to treat the brain with all due respect to its natural processes.

For an extensively-referenced compendium of nutrient-based approaches for bipolar disorder, see my book, Natural Healing for Bipolar Disorder.
Available here.
You may also be interested in Natural Healing for Schizophrenia.
Available here.

This information is presented for educational purposes only, and is not intended for diagnostic or treatment purposes. If you need treatment for mood disorder or any other medical condition, please consult a knowledgeable physician.
Warning: Changes in medication can trigger episodes which are worse than the initial illness. If changes are desired, please consult a knowledgeable doctor. Orthomolecular doctors usually add the new nutrients to the prior drug regimen. They then reduce meds in very gradual steps, and each stage, only when enough improvement on the nutrients allows it. 

The Power of Nutrients; Edelman article

How important can nutrients be? Can they really do much for severe mental health symptoms? Two old illnesses, whose vitamin cures have been used by modern medicine for the past hundred years, will serve to provide an intuitive glimpse into the potency of nutrients in brain function.

Vitamin C and Scurvy

 

Consider first, scurvy, the disease of the ancient pirates, a prolific killer of olden-day sailors on long sea voyages. Symptoms included easy bruising, internal bleeding, roughening skin, and wounds which would not heal. Teeth would loosen and fall out. Scurvy also caused profound anxiety and depression, overwhelming fatigue, insomnia and, eventually, in some cases, psychosis. Late stage scurvy often resolves into fever, convulsions, and death.

Scurvy has been known for at least 2000 years, and periodically, people have tried various fresh food cures, only to lose that knowledge in subsequent generations. In the twentieth century, treatment with sources of vitamin C caught on more universally. Sufficient C not only stems the physical changes, but also reverses the often-severe mental symptoms.

Note again: Vitamin C, all by itself reverses the psychosis and mood changes of scurvy! Interestingly, many institutionalized psychiatric patients have vitamin C levels close to that found in people with scurvy.

Vitamin B3 (Niacin) and Pellagra 

Secondly, let us look at pellagra, an illness characterized classically by the 4Ds: Dermatitis, Diarrhea, Dementia and Death. That is: various skin and gastrointestinal symptoms, along with increasing weakness and depression, mood instability, aggression, insomnia, confusion eventually resolving into dementia and, in some cases, a schizophrenia-like psychosis.

In the early 1900s, liver, and then, its active ingredient, niacin, was found to cure pellagra. A few hundred mg. of vitamin B3, over several weeks, reversed the unstable mood, the irritability and violent disposition, and the pellagren psychosis.

Since then, orthomolecular psychiatrists have found niacin helpful in many cases of schizophrenia and depression, and critical in up to 90% of cases of paranoid schizophrenia.

If such nutrients can cure the severe mental symptoms of scurvy and pellagra, then perhaps they also have the power to address those same symptoms in psychiatric disorders.

About the author

Eva Edelman is a health researcher and the author of two widely-acclaimed compendiums:

Natural Healing for Bipolar Disorder: A Compendium of Nutritional Approaches

Natural Healing for Schizophrenia and Other Common Mental Disorders

For more info on these books, see http://www.boragebooks.com

NAMI/ Lane County/ Spring 2013 Newsletter

VI.d. Histamine, hyperthyroid, undermethylation

Many histadelics (undermethylated, high histamine and folate individuals) experience overactive thyroid (others, underactive). Possible mechanisms for the elevated thyroid found in some histadelias:

Histamine can increase thyroid hormone. 

Histamine triggers TRH release, increasing thyroid hormones.
The thyroid, in turn, may block histamine degradation and increase sensitivity to histamine, worsening the histadelia.*  (Mariano)
* On the other hand, it can reduce mast cells, and decrease histamine release.

The low NE activity, common in histadelia, can increase thyroid hormones.

Norepinephrine (NE) and thyroid have the same precursor, tyrosine. The relation between NE and thyroid can be reciprocal, with elevated thyroid compensating for decreased NE.  (Swann,
Becker)

Autoimmune thyroid, which may be due histadelia, can initially cause sporadic hyperthyroidism.

See  VI.b. Autoimmune thyroid, histadelia and glutathione


Note: Thyroid status can also be largely independent of the histadelia.

For a wider view of thyroid, histadelia, and bipolar disorder, you may want to see my book, Natural Healing for Bipolar Disorder
                available here.

To contact me, click here.

VI.c. Low thyroxine, histadelia and B12

BH4 (biopterin) is required in converting tyrosine into thyroid hormone, dopamine and norepinephrine; and for forming serotonin from tryptophan.   If, in the homocysteine-to-methionine step  of the methylation cycle,  methyl folate cannot give up its methyl to B12, you get what is called a folate trap. Methyl folate accumulates (actually, 5-methyl-hydrofolate), and cannot break down into usable folate (5HTF), needed in creating biopterin. (Scroll up to the diagram at the top of this link). 

Again, if BH4 is limited, then so are thyroid hormones, and key antidepressant neurotransmitters.
So you get undermethylation and low thyroid, along with low dopamine, norepinephrine and serotonin.

In other words, we have here a subset of histadelics with difficulty transferring methyl from folate to B12, prone to low levels of thyroxine (T4).

Odd, isn't it, when histadelics generally have high metabolism. Perhaps, in some cases, T3 compensates.

For more on the folate trap, look here.

For a wider view of thyroid, histadelia, and bipolar disorder, you may want to see my book, Natural Healing for Bipolar Disorder
                available here.

To contact me, click here.
 

VI.b. Autoimmune thyroid, histadelia and glutathione

Histadelics (undermethylated, high folate individuals) can be either high, low or normal thyroid. What follows is a possible association between undermethylation and autoimmune thyroid.

1 Undermethylation is commonly associated with low glutathione
Almost all histadelics  are low in glutathione, a critical antioxidant, because:
—  An efficiently functioning methylation cycle is needed to supply precursors of glutathione as well as other important sulfur antioxidants. 
— Also, in some, due to specific problems in feedback mechanisms between the methylation cycle and transsulfuration pathway.

2 Low glutathione may foster thyroid autoimmunity
The thyroid uses hydrogen peroxide to create thyroid hormones. Glutathione peroxidase then detoxes the hydrogen peroxide. If glutathione is lacking, however, the hydrogen peroxide, a potent free radical, will react with thyroid proteins. The immune system may then fail to recognize these altered proteins as normal constituents of the thyroid, and launch an autoimmune attack.   C Duthoit (2001)
suggests this scenario as a possible etiology of autoimmune thyroid.

In this vein, Dr. Rich van Konynenburg reports that thyroid function improved markedly in a number of his chronic fatigue, autoimmune hypothyroid patients, upon methylation and glutathione support. They find glutathione stimulating, perhaps due to enhancement of thyroid function

-- suggesting caution with glutathione during episodes of thyroid hyperactivity (and perhaps mania) that can occur with early thyroid autoimmunity.

For a wider view of thyroid, histadelia, and bipolar disorder, you may want to see my book, Natural Healing for Bipolar Disorder
                available here.

To contact me, click here.

VI.d. Thyroid / Histamine Interactions

Chronic elevated histamine is one of the chief means of diagnosing histadelia, the most common biotype in bipolar disorder. Histamine interactions with the thyroid are complex, and not well-explored. Here is some food for thought:

The thyroid can either increase or decrease histamine:

— The thyroid may suppress the brain's histamine release and decrease its histamine-containing mast cells.
— Or increase body sensitivity to histamine and block its degradation.
 Sabria 1987, Uhpadhyaya, 1993,  Mariano 2009

Histamine may alter thyroid function

Histamine is known to strongly influence hypothalamus regulation of cellular metabolism, energy production and food intake. The thyroid is a major target gland in hypothalamic governance of  metabolism and energy production.
 Elmhar 2006,  Sakata 1997, Masaki 2001

Allergies and associated histamine release may be hard on the thyroid

Allergic reactions, which cause the profuse mast cells of the thyroid to dump histamine, and perhaps iodine, may thereby interfere with thyroid function. (Elmhar, Do low thyroids suffer more with allergies?)

Histamine may contribute to thyroid autoimmunity

Histamine-releasing antibodies are often found during increased thyroid autoimmunity, suggesting histamine may contribute to the immune attack on the thyroid (Mariano, 2009) -- perhaps via inflammation and increased permeability. (Melander 1975)


For a more comprehensive view of thyroid, histamine, and bipolar disorder, you may want to see my book, Natural Healing for Bipolar Disorder
                available here.

To contact me, click here.

Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Each person's biochemical requirements tend to be unique. So if you need treatment for bipolar, thyroid disorder or any other medical condition, please consult a knowledgeable physician.

VI.a. Thyroid, histamine and methylation in bipolars

Thyroid disorders, like histamine imbalances, pervade the bipolar population. Metabolism is low in histapenia and hypothyroid, high in histadelia and hyperthyroid. Some histamine/thyroid symptoms match up, others do not. The relationship of thyroid to histamine and methylation is complex, and not well explored.

The following posts will look at this relationship, particularly as regards bipolars.


For more on thyroid and bipolar disorder, you may want to see my book, Natural Healing for Bipolar Disorder
                available here.

To contact me, click here.

V. Hyperthyroid and Bipolar Mania

High thyroid can interact with, trigger, or intensify mania, (Nath 2001, Escamilla 2001)  and can also increase switching on antidepressants. (Bottlender, 2000). Even levels in the high-normal range can contribute to the development of mania. (Lee 2000, Roca 1990)

Joyce (1991), for instance, reported more than one-third of manics with elevated thyroid, and in the other two-thirds, various individuals with higher thyroid in mania than depression. Moreover, a number of researchers have suggested lithium’s anti-thyroid effects may underly its benefit to mania.
In some manics, however, thyroid can test low.

Mental symptoms that can be common to both hyperthyroid and mania

High irritability, tension, emotional instability, explosiveness, anxiety; exhilaration, increased motor activation, restlessness, tremors, hyperactivity, insomnia and other sleep problems; and, in some cases, erratic bizarre behavior, mood swings, impulsive destructive tendencies, psychosis, paranoia.

Eventually, perhaps, exhaustion or depression

Over time, hyperthyroids may succumb to depression and social withdrawal, perhaps due to an exhaustion caused by extended thyroid overstimulation. Similarly (although usually sooner), manic overstimulation eventually gives way to depression.


To get a comprehensive view of the interaction with bipolar disorder, you may want to look through my book, Natural Healing for Bipolar Disorder
                available here.

To contact me, click here.


Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Each person's biochemical requirements tend to be unique. So if you need treatment for bipolar, thyroid disorder or any other medical condition, please consult a knowledgeable physician.

IV.a. Autoimmune thyroid and bipolar disorder

Autoimmune Thyroid (Hashimoto's disease)

An estimated 50 to 90% of cases of hypothyroidism result from anti-thyroid antibodies. Hashmimoto's antibodies seem to be more common in people with bipolar depression, mixed state, and rapid cycling (and to a lesser degree, in other affective disorders) than in the general population.

Symptoms

Symptoms usually start with neck tenderness, and may be otherwise unnoticeable. Depression, memory and concentration problems may be the next to emerge.
Thyroid activity may cycle initially, so you can get periods of insomnia, anxiety, inner tension, panic attacks, hypomania, rapid heart beat, etc. due to thyroid hyperactivity. In some cases, overactivity is severe, creating hashitoxicosis.
Over years, the ongoing attack on thyroid tissue suppresses function causing hypothyroidism, with typical symptoms such as weight gain, chronic depression and fatigue, constipation, kidney and heart complications, etc.  (See previous post)

Potential Causes 

Psychosocial stressors.
Overstimulation with iodine or certain drugs.
Chronic exposure to fluoride, chlorine.
Toxic exposure.
Immune challenge (e.g., Candida, Epstein Barr).
Undermethylation and lack of glutathione
More on this later.


To get a more comprehensive view of the implications of thyroid function, and other endocrine status on bipolar disorder, you may want to look through my book, Natural Healing for Bipolar Disorder,
                available here.

To contact me, click here.


Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Each person's biochemical requirements tend to be unique. So if you need treatment for bipolar, thyroid disorder or any other medical condition, please consult a knowledgeable physician.

III. Low Thyroid and Depression

Thyroid: Mood and Cognitive Symptoms

Thyroid imbalances, particularly hypothyroid (low thyroid), pervade the depressed population.
Conversely, depression (and low energy) is a major symptom for almost all hypothyroid patients, even if only mildly low thyroid. (Fardella 2000, Pies 1998, Placidi 1998, Prange 1996, Musselman 1996)

Typical mental symptoms also include: apathy, loss of interest or pleasure, cognitive slowing, difficulty concentrating, suicidal ideas, memory problems, weakness, pervasive fatigue (may literally sleep one's life away), emotional instability, anxiety, perhaps panic, delusions and fears, suspiciousness and resentment.

Greater Severity and Myxedematous Madness 

Progressive hypothyroidism (myxedemia) steadily slows mental and physical functioning, compromising memory, concentration, comprehension, energy, and reflexes.
Before hormone treatment developed, up to 50% developed a psychosis, termed, myxedematous madness.
Symptoms could include melancholia, mania, and psychosis. Also,  slowed thinking, dementia, morbid dreams, obsessions, frightening hallucinations, persecutory delusions, paranoia, suicidal ruminations, along with physical symptoms of low metabolism.   (Gull 1873,  Clinical Society of London 1888,  Asher 1949)

Missed Thyroid Diagnoses

Psychiatric hypothyroid symptoms frequently precede physical, often leading to misdiagnosis as depression, and incorrect treatment. (Asher 1949, Reed 1977, Boillet 1998)
Low thyroid decreases cerebral glucose metabolism and blood flow (Marangell 1997), suppresses catecholamine activity and receptor sensitivity (Mano 1998), and is associated with more lengthy, frequent and severe depressions. Subclinical or clinical hypothyroidism is especially common in antidepressant-resistant affectives. (Frye 1999)

Note: Physical Symptoms

Weight gain, increased fat, difficult to reverse unless thyroid activity improves. Appetite changes.
Dry, puffy, rough skin; flaky acne. Pallor, yellow tinge (due to difficulty metabolizing carotene).
Water-logged tissue, e.g., ankles, face, especially under the eyes. 
Missing outer third of eyebrows. Eyebrows may be permanently raised to keep lids open.
Brittle, easily broken nails. Thinning, dry, brittle, hair. 
Vision problems, night blindness. Hearing problems.
Hoarseness, slurred speech, tongue thick and swollen, difficulty swallowing.
Anemia, poor circulation, cold sensitivity; perhaps also intolerant to heat.
Joint pain or stiffness, arthritis. Fatigue after minor exertion. Muscle weakness, aches, cramps.
Headaches, migraines.
Indigestion, gas, chronic constipation. Sensitive to drugs and toxins.
Prone to allergies, Candida, hypoglycemia, diabetes.
Low libido, PMS, fertility problems. Menses tend to be irregular, profuse, painful.
Shortness of breath, chest pain, slow pulse. Low blood pressure; but eventually too high, elevated cholesterol, atherosclerosis, heart disease. Prone to lung disorders.

To get a comprehensive view, you may want to look through my book, Natural Healing for Bipolar Disorder
                available here.

To contact me, click here.


Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Each person's biochemical requirements tend to be unique. So if you need treatment for bipolar, thyroid disorder or any other medical condition, please consult a knowledgeable physician.

II. Thyroid and bipolars: Some Iodine Issues

I. Thyroid and Bipolar Disorder

The thyroid gland is crucial to metabolism, growth and immunity, as well as supporting heart and kidney function, bone development, and maturation of the nervous system. Thyroid is also critical to cognition and mood.

In fact, thyroid hormones have been used to augment antidepressants and convert nonresponders, and to treat certain rapid cycling and hypomanic patients unresponsive to other treatments (though careful medical evaluation is essential, as thyroid hormone may promote mania).

Thyroid status in bipolars

Bipolars frequently exhibit thyroid underactivity or sometimes other thyroid conditions.* (Lasser 1997, Pies 1998)  Moreover, two of the major mood stabilizers (lithium and carbamazepine) may suppress the thyroid further. (Lazarus 1998)

In some bipolars, thyroid activity cycles with affective state.  Bipolars may be particularly sensitive to such fluctuations, even when within the normal range. (Cole 2002)  Cognitive function, for instance seems to be significantly linked to thyroid status, rather than lithium levels. (Tremont 1997)

Barnes (1976) warned that many patients medicated for depression, anxiety, and so forth, have undetected thyroid dysfunction, causing mood symptoms. Unfortunately, effective thyroid  status is often obscured by distorted interactions of the hypothalamus/pituitary/thyroid axis, and by difficulty determining peripheral sensitivity to thyroid.**(Pies 1998)

* Even as compared to the general psychiatric populations, in which thyroid problems are common. (Gloger, 1997, Fardella 2000, Placidi 1998)
** For example, you can get high thyroxine, with an elevated pituitary TSH nonresponsive to regulatory feedback, so continuing to stimulate the thyroid further. Along with high thyroid symptoms of, for example, weight loss, rapid heart beat, etc., the patient may manifest selective insensitivity to T4 in mood-modulating neural pathways, fostering the low thyroid symptom of depression. Labs also will be contradictory: with high T4, suggesting hyperthyroid; high TSH, hypothyroid. Thus neither effective thyroid status nor appropriate treatment will be readily apparent.

Affective symptoms in thyroid disorder patients

Thyroid dysfunction alters mood (as well as cognition and behavior), (Lasser 1997, Loosen 1987, Prange, Whybrow 1987, Tremont 1997)  typically creates affective symptoms, (Gibson 1962, Graves 1843) and is associated with increased incidence of depression, dysthymia, bipolar disorder, cyclothymia, panic disorder, phobia, and obsessive compulsive disorder. (Placidi 1998)

Hypothyroidism characteristically creates a depressive syndrome; even subclinical hypothyroidism may be associated with mood cycling, depression, and poor or slow response to affective treatment. Autoimmune thyroiditis is often associated with depression (especially postpartum), and with rapid cycling. Hyperthyroidism creates symptoms of, and contributes to, mania. (Pies 1998)

Nonetheless, the precise impact of thyroid activity can vary from one individual to another. (Loosen 1987)

I have excerpted the above post from the first page of a 32-page section on thyroid in my book, Natural Healing for Bipolar Disorder (copyright 2009).

To get a comprehensive view, you may want to look through my book, on bipolar disorder
                available here.

To contact me, click here.


Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Each person's biochemical requirements tend to be unique. So if you need treatment for bipolar, thyroid disorder or any other medical condition, please consult a knowledgeable physician.

Help Us Spread the Word

Help people find out about natural approaches for bipolar and schizophrenia by providing a link on your website to http://boragebooks.com
and/or to http://naturalhealingforbipolardisorder.blogspot.com
Thank you for your support.
Eva Edelman

Histadelia and Other Approaches for Bipolar Disorder

Readers interested in reviewing entries for histadelia (brain undermethylation and folate accumulation) can start at the 12/3/10 post on histadelia and bipolar depression and go on from there.
Most of the posts which follow are on histadelia, although from July 21 to Aug 20, 2011,  I talk about histapenia, in many ways the opposite biotype.
The early histadelia posts are more basic. Recently, I have turned the focus to histadelia biochemistry.
Remember, though histadelia is the largest biotype in bipolars, any combo of pyroluria, histapenia, allergies/immune dysfunction, oxidative stress, metal metabolism issues, Candida, blood sugar problems, hormone imbalances, toxicity, neurological disorders, etc., may be the relevant factor(s) for a specific individual.
 
To get a comprehensive view, you may want to look through my book,  Natural Healing for Bipolar Disorder
                available here.

To contact me, click here.


Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Each person's biochemical requirements tend to be unique. So if you need treatment for bipolar, or any other medical condition, please consult a knowledgeable physician.

Notes: Histadelia, Sulfur, and Autism

Notes on histadelia, sulfur metabolism, and autism spectrum chemistry

1 Undermethylation. Dr. William J. Walsh (1999) originally found,* in reviewing 20,000 labs taken on hundreds of autistic individuals, that 90% showed brain undermethylation (histadelia). Drs. S Jill James and Richard Deth have since confirmed this. Dr. Amy Yasko's nutrigenomic research, which targets specific enzymes causing methyl metabolism problems, further confirms this chemisty. (Also see Nutrigenomics discussion, here.)

2 Sulfur Metabolism. The research of Dr. Rosemary Waring (2000) first drew attention to sulfur pathway problems in most autism spectum patients, specifically inadequate sulfation and PST activity, probably due to insufficient sulfate, and overzealous excretion. Follow up work suggests high sulfite, CBS overactivity, and other sulfur issues are also prevalent.

3 Metal metabolism. But unlike most other histadelics, autistics also tend to metal metabolism dysfunction, with elevated copper and toxic metals, and zinc and B6 inadequate. This aggravates oxidative stress further, even beyond what you find in other psych patients. (Walsh)

4 Severe oxidative stress. Profound oxidative stress** and metallothionein depletion*** at fetal and infant levels, slows and distorts brain development. Oxidative stress and sulfur pathway issues also impair brain and gut barriers and protein digestion. (Walsh)

5 Triggers. Later insult -- e.g., injection of toxic metals into the blood stream (as in mercury-containing vaccines),  chronic reactivity to gluten and dairy, or ongoing excitotoxic exposures -- can attack the already beleaguered brain all too readily, compounding toxicity and inflammation, and further fueling oxidative stress, thus triggering onset of identifiable symptoms, and a progression of developmental problems.

* Data presented at a DAN think tank in Cherry Hill, NJ, 1999, also showing low zinc and B6, high copper and toxics.
** Walsh reports extreme oxidative stress, with low glutathione,  low cysteine (its precursor), low selenium (its cofactor), and low SOD (a key endogenous antioxidant).
*** Metallothioneins (MTs) are the enzymes critical to transport and removal of  divalent heavy metals (e.g., mercury, cadmium, arsenic), and the regulation of zinc, copper and selenium. Undermethylation may compromise MT production.

Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Even within the histadelic subgroup, each person's biochemical requirements tend to be unique. So if you need treatment for autism, bipolar, or any other medical condition, please consult a knowledgeable physician.
 
For info on the role of undermethylation in bipolar disorder, see my book, Natural Healing for Bipolar Disorder
                available here.

To contact me, click here.

Bipolar Histadelia and Sulfur: V-e. A Summary.

Histadelia (brain undermethylation) is the primary imbalance in an estimated 35% of bipolars. Most histadelics have problems in the trans-sulfuration pathway, because it is so closely connected to the methylation cycle.  On the one hand, methylation cycle distortions change precursor availability and enzyme activation in the trans-sulfuration pathway. On the other, insufficient sulfur antioxidants and high oxidative stress, will interfere with formation of methyl-B12 and divert too much homocysteine into forming sulfur compounds, compromising the methylation cycle. (Walsh)
To resolve sulfur issues, increasing glutathione and other antioxidants turns out to be sufficient for some histadelics. However, in a significant number of cases, attention to some of the other trans-sulfuration issues we have been discussing becomes necessary.
See part 4 and 5 of this diagram.

How trans-sulfuration problems can impact histadelia and bipolar symptoms:

1 Skyrocketing oxidative stress can compromise brain methylation. Causes may include:
— overactive SUOX, creating a buildup of ammonia and toxic sulfurs, and fostering excitotoxicity
— a buildup of toxic sulfur compounds due to poor sulfite to sulfate conversion.
— drastically reduced formation of glutathione and sulfur antioxidants

Glutathione then becomes much less available to connect to B12 and enable formation of methyl-B12. Blocking this step, formation of methionine and SAM, and methylation of DNA and proteins are impeded.*
For a review of undermethylation symptoms, see here and here. 

2  Poor sulfation compromises normal metabolism of mood-altering molecules and toxins.

— If sulfate is low (whether due to excess urinary loss, or reduced sulfate formation), then sulfation tends to be compromised. This leads to phenol accumulation and increased sensitivity reactions, inflammation,  and oxidative stress.
—  Poor sulfation can also compromise amine metabolism. This can lead to an accumulation of stimulatory neurotransmitters and altered regulation of estrogen and cortisol, contributing to anxiety, tension, irritability, insomnia, mania, etc.

3 Formation of taurine may be compromised.
—   Taurine is a critical inhibitory neurotransmitter, lack of which would tend to destabilize mood, and foster overstimulation, neurological instability, tension, irritability, etc.

4  Increasing toxicity compromises brain function.
Toxicity can be due variously to lack of sulfur antioxidants and glutathione, poor metabolism of sulfurs, phenol and amine accumulation, overproduction of ammonia (which creates brain fog) and sulfur compounds, excitotoxicity and profound oxidative stress. Toxicity can attack receptor accuracy, second messaging, axonal transmission, neurotransmitter systems, astrocyte activity, as well as specific brain structures. Functional deterioration may manifest as learning or behavior disorders, depression, mood instability, OCD, dementia, etc.,  and in severe cases in the very young, especially if metal metabolism is suppressed, autistic symptoms. (See Notes, next post.)

*The betaine pathway may take up some of the slack in some individuals. Nevertheless, problems with the transsulfuration pathway generally foster undermethylation.


Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Even within the histadelic subgroup, each person's biochemical requirements tend to be unique. So if you need treatment for depression, mania, bipolar, or any other medical condition, please consult a knowledgeable physician.
 
For info on the role of histadelia in bipolar disorder, see my book, Natural Healing for Bipolar Disorder
                available here.

To contact me, click here.

Histadelia and Sulfur: Part V-d: Phenol sensitivity

What are Phenols?
Phenol is C6H5OH. It alone is toxic, as are certain phenol compounds. However, phenols are also found in many healthful fruits, vegetables, herbs, seeds and nuts. And certain phenols are, variously, important in normal metabolism, including metabolism of adrenal stress hormones; in countering oxidative stress, inflammation and toxicity;  and, possibly, as a protective agent in diabetes, cancer, and aging.
Phenols include flavonoids (the coloring matter in plant foods, known for antioxidant and anti-inflammatory properties),  resveratrol (in grape skin), tocopherols (vitamin E), carotenoids (which have vitamin A-like activity), and salicylates (this guide lists salicylate-rich foods), as well as the flavoring compound in raspberries, the agent which makes cayenne hot, the source of the smoky/ pungent scent in many perfumes, and a breakdown product of hemoglobin.

Sulfation of Phenols
Phenol accumulation, however, presents toxicity issues. Normally, a process called sulfation* attaches sulfate to the phenols in food and chemicals, making them less toxic, and facilitating elimination. Specifically, the enzyme, PST (phenol sulfur-transferase), sulfo-conjugates phenols, creating phenol-sulfates.
The basic chemistry is:    phenols --via PST-- yield phenol-sulfates
* Sulfation is also one of the major processes in liver detox activity, targeting various compounds, not just phenols.

Phenol Sensitivity
Too few sulfates, too many phenols, or downregulation of PST allows phenols to accumulate instead of being detoxed and eliminated via sulfation. Thus, phenol sensitivity is a good indicator of sulfation problems.

The development of phenol sensitivity is accelerated by a leaky gut, which would allow poorly digested phenol foods into the bloodstream. As mentioned in the previous post, insufficient sulfates also means poor mucin creation, compromising gut integrity.

Amine Sensitivity. Accumulation of stimulating neurotransmitters and hormones.

People who have problems with phenols also often show sensitivity to amines, which also need sulfates and sulfo-transferase enzymes to inactivate them. Amines include the antidepressant neurotransmitters: serotonin, epinephrine, norepinephrine and dopamine; the amino acids, one of the metabolites of thyroid hormone, and tyramine. 
Sulfation also seems to be needed to metabolize or regulate estrogen and adrenal stress hormones. 


 In summary, a lack of sulfates, subfunctional sulfo-transferases, and too many phenols and amines taxing the system, leads to phenol and amine accumulation, often producing sensitivity. (See Rosemary Waring, PhD,  on amine sensitivity), This biochemistry also increases overall toxicity, excitotoxicity, and oxidative stress, with profound effects on brain function. Moreover, inadequate sulfation prevents the body from adequately removing stimulating neurotransmitters and hormones, thereby increasing the tendency to anxiety, insomnia and mania.

CONSIDERATIONS (John Pietryka, ND, presents a good summary of specific effects, from which the following is derived)

Sensitivity reactions to salicylates and other phenols can include affective symptoms, such as:

Mood swings, depression.

Hyperactivity, irritability, sudden anger, overstimulation, hypomania.
Other mental and physical symptoms:
Delusions, phobias, dysperceptions, feelings of unreality, perhaps hallucinations.
Sensitivity to light and sound, ringing in the ears. Dark circles under the eyes.
Sleep problems, night sweats.
Memory and concentration problems, episodes of blank mind, disorientation, vertigo.
Socialization problems (associated with low CCK activity).
The following physical symptoms:
Rash, eczema, red face, hives, feeling of something crawling on the skin, other skin conditions.
Frequent urination or urinary retention, dehydration.
Nausea, gastrointestinal symptoms, gall bladder problems.
Hyperventilation, tachycardia, racing pulse, breathing issues, excess or suppressed perspiration.
Muscle or joint aches. Migraines.

Family history of:
Migraines, allergies, chemical sensitivity.
Perhaps, Alzheimers, Parkinsons, motor neurone disease, or cirrhosis.
(Similar to whats found in histadelia.)

Look for:

Hyperactivity or lethargy when taking Tylenol, and/or reactivity to aspirin.
Urinary loss of potassium and sodium bicarbonate.
Toxic metal buildup. Problems eliminating toxins.
Low plasma sulfate, often high urinary levels.

TREATMENT APPROACHES  (Petryka,   Roberts,    and here)

Potentially helpful nutrients:

Molybdenum (especially if sulfite conversion is a factor). 
B6 can inhibit PST, but generally supports sulfoxidation. Adverse symptoms reduced if 1:1 with magnesium. (See: Rosemary Waring, PhD)
Other B vitamins are often useful.
Epsom salt bath or cream, as relevant. (See Kurt Woeller, DO)
Additional sulfate sources such as taurine and glucosamine sulfate may or may not help. Similarly, for sulfur foods. Avoid sulfites.   
Pancreatic digestive enzymes (suppressed by low sulfate), which break down fats, proteins, nucleic acids and carbs, as relevant.
Enzymes which digest veggies, fruits, nuts and grain (e.g., breaking down xylose, cellulose, glucans, phytins, galactose, and carbs), as relevant.  
Possibly, baking soda.  (Interesting anecdote on suggestions by Rich Van Konynenburg, PhD)
Possibly, cranberry juice (anecdotal). (John Petryka, ND)

Supporting sulfation after long impaired can cause intolerable detox reactions and discourage use of nutrients needed for healing.  Which is why certain nutrients (even glutathione) may have to be introduced gradually. 

Issues with otherwise healthy foods  (John Petryka)

Salicylates and other phenol-rich foods (apple, citrus, chocolate...) use up, sulfate. Many also inhibit sulfation itself.* Similarly, amine-rich foods (tyramine, etc.), use up sulfate.
Boron (found in apples pears, legumes, nuts, leafy greens, grapes) interferes with phenol breakdown.
* Oranges, spinach, radish, grapefruit, beet, pepper, squash, vanillan, tomato, food color as well as flavonoids, inhibit sulfating enzymes. 

Nevertheless, such foods and nutrients clearly convey important health benefits, so are restricted mainly at the beginning of treatment (until reasonable sulfation can be established), and mainly to the extent to which they are causing significant adverse symptoms. 

Restrictions vary with the individual. People commonly react to certain foods, but not others. Reactive foods may need to temporarily be avoided or, at least, eaten less frequently, and in smaller amounts. Eventually though, with enough sulfation support, reactivity should diminish enough so that most such foods can be eaten in reasonable quantities.

Avoid:

Eliminate unnecessary sources of phenols such as food additives (dyes, flavors, preservatives), perfumes and room scents, coal-tar-derived (not high-quality) vitamins, perfumes and certain drugs (notably, the salicylate of aspirin).

See also, previous post.

Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Even within the histadelic subgroup, each person's biochemical requirements tend to be unique. So if you need treatment for depression, mania, bipolar, or any other medical condition, please consult a knowledgeable physician.  

Next post:  Applicability of sulfur pathway issues to histadelic bipolars.

For info on the role of histadelia in bipolar disorder, see my book, Natural Healing for Bipolar Disorder

   available at  boragebooks.com/orderBooks.html

Histadelia and Sulfurs: Part V-c: Sulfites to Sulfates

Another subset of high-oxidative-stress, undermethylated bipolars have problems converting sulfites to sulfates. Overloaded sulfites transform into toxic sulfur compounds which increase the burden on antioxidants and detox agents, using up glutathione. Moreover the sulfates which should have been formed are important antioxidant and detox agents, which help spare glutathione. So, again, we can have difficulty joining methyl to B12, impeding formation of methionine and SAM, thereby fostering undermethylation.

Difficulty metabolizing sulfites to sulfates can be due to

A simple lack of molybdenum.

Chronic overload of sulfur compounds.

Underactivity of the enzyme, SUOX (sulfite oxidase) which catalyzes the oxidation of sulfite to sulfate.  

The basic chemistry is 
Sulfite + molybdenum + B6 (P5P) + SUOX  yields  Sulfate
See Methionine cycle, step 4, lower half of diagram. 

or lower right of this diagram

CONSIDERATIONS.
Check for elevated urinary sulfites.
Doing okay with sulfates and taurine (which converts to a sulfate without using SUOX), but reacting to sulfur supplements and foods, especially eggs, suggests sulfite to sulfate conversion problems.

Sulfates are needed in nerve, bone and cartilege formation, mucin creation, liver detox, and catecholamine inactivation. Thus, the following conditions may be associated with low sulfate formation (or with low sulfation):

—Overstimulation: Sulfation inactivates thyroid hormone and catecholamines (e.g., dopamine).  (Interesting overview at http://what-when-how.com/molecular-biology/sulfation-molecular-biology/)
— Inflammation.
—Migraines.
—Arthritis and other joint/cartilege maintenance and repair problems (think MSM and glucosamine).
—Digestive symptoms: leaky gut, irritable bowel, low stomach acid, gall bladder hypofunction (problems with fats), low digestive enzymes, constipation.

TREATMENT APPROACHES  (Petryka,  Roberts)

Molybdenum (in legumes) helps form sulfate (as well as BH4 -- see previous post). Low uric acid or intolerance to alcohol can also suggest low molybdenum.
P5P (a form of B6) may also be needed.
However, too much of either can be counterproductive.
Hydroxy B12, boron, and vitamin E (along with the molybdenum 2x/day) may help increase SUOX activity. (Roberts)
Restict/avoid sulfites. (An upbeat non-medical discussion of sulfites here).
 

Sulfates, if depleted, will be helpful: 
—Epsom salt (magnesium sulfate).  Can be added to baths, but this is contraindicated if there is any danger of falling asleep in the bath, or if taking antipsychotics, anxiety or sleep meds, or consuming alcohol or other suppressants. An epsom salt foot soak, epsom sprays, or creams may be used instead.  Or a combo of sources.  E.g., see enzyme stuff, about half-way down the page. 

—Taurine.
—MSM, glutathione sulfate, or NAC may or may not help.

Phenol and salicylate restriction is often indicated as sulfates are used up in their metabolism. More on phenols and salicylates next post.

Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Even within the histadelic subgroup, each person's biochemical requirements tend to be unique. So if you need treatment for depression, mania, bipolar, or any other medical condition, please consult a knowledgeable physician. 

For info on the role of histadelia in bipolar disorder, see my book, Natural Healing for Bipolar Disorder

   available at  boragebooks.com/orderBooks.html