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

Bipolar Nutrients: GABA/Glutamate Balance, Vitamin K2, Salicylates, Ketones

As an introduction to GABA, let's look at the perspectives of EJD. The responses to his post are also interesting.

In brief, EJD proposes:
1 GABA is the most important factor in bipolar. Low GABA/glutamate ratio fosters bipolar mania
2 Possible ways to increase GABA: valerian, theanine, taurine, skullcap, kavakava, glutamine,  calcium/magnesium, relaxation techniques. And, of course, GABA (if available), 
3 A low carb, ketogenic diet increases GABA. Vinegar before meals, acts similarly, but can gets used up too fast.
4 Vitamin K2 (modest amounts) helps neutralize glutamate, metabolizing it to a bone-building compound.
5 Restrict/avoid salicylates -- by altering dopamine, activating NMDA receptors, and inhibiting GABA -- elevate, then sink mood, and often, as well, cause brain fog (B12 helps).


He also notes that:
Dopamine is the major antidepressant neurotransmitter. Serotonin is more of a regulator of dopamine and mood, than a direct antidepressant.
Genetic changes in enzymes*  that break down catecholamines, may favor preserving adrenalin over dopamine, lending irritability to any manias.

*EJD points to COMT; a responder suggests MAO.

Go to EJD's post for specifics.

I include EJD's ideas here as an interesting intro to GABA, worth thinking about. But do keep in mind that this is just one person's experience and conjectures, and that EJD is neither a physician nor a medical researcher.
And remember that bipolar treatment must be tailored to each individual's unique biochemical requirements.  Not all bipolars respond well to GABA, etc..  More in the next post.

Reminder: If you need treatment for bipolar disorder, or any other medical condition, consult a knowledgeable physician. In some cases, this will be an orthomolecular or other nutritionally-oriented physician.