Ray Peat Email Advice Depository

Ray Peat said:

A combination of eggs and oysters would cover the main nutrients, but not as well.

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Ray Peat said:

The ratio of calcium to phosphate is more important than the absolute amount of calcium. 4 ounces would usually be enough.

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Ray Peat said:

If thyroid function is good, and inflammation is low, about 5 mg of DHEA is probably safe, but I think pregnenolone and cynomel would probably be as effective.

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Ray Peat said:

Have you kept a record of your (waking and midday) temperature and pulse rate? How were you using the progesterone?
Did your blood glucose or insulin requirement change while using those? Has your vitamin D been measured?

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Ray Peat said:

I think a combination thyroid product (such as Armour thyroid USP, Thyrolar, Cynoplus, etc.) might work better. Clots and pain, and the low temperature, imply that your thyroid function was still very low. What has your TSH level been?

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Ray Peat said:

The cynoplus tablets can be divided into pieces so that each dose of T3 is similar to the amount you were taking in cytomel. In diabetes, when cells aren't getting enough glucose, T4 can't be converted to the active T3, and so it can build up in the body to levels that interfere with metabolism, but the advantage of a combination is that T4 inhibits TSH, and TSH is responsible for many of the symptoms.

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Ray Peat said:

Pure colorless highly distilled alcohol is the safest. It can have antioxidant effects, but in some people it can interfere with the respiratory enzymes and lower blood sugar. Fructose is protective against some of its toxic effects.

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Ray Peat said:

Hypothyroidism is the basic cause of heavy menstruation. Things strong enough to kill an embryo can't be harmless to a person.

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Ray Peat said:

PThere are several articles relating to diabetes on my website. Polyunsaturated fats damage the pancreas and increase stress hormones, while glucose stimulates the renewal of insulin-secreting cells. Fruits provide minerals that help to regulate glucose metaboiism, and help to regulate thyroid function.

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Ray Peat said:

Diabetes usually causes some interference with the formation of the active thyroid hormone, leading to increased cortisol relative to progesterone and DHEA. Those vitamins, and pregnenolone and progesterone help to strengthen capillaries.

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Ray Peat said:

Pure aspirin is available by the kilogram. 30 mg of pregnenolone without excipients is o.k.; niacinamide should be tried for allergy reaction, but if there's no reaction, 50 to 75 mg with each meal might help to regulate glucose.

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Ray Peat said:

Yes, white bread is usually artificially leavened, and so contains unmodified starch and gluten.

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Ray Peat said:

Yes, it's definitely a problem for people who are sensitive to gluten. Home-made bread, that's soaked for about 12 hours during leavening, is much safer than the typical commercial bread.

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Ray Peat said:

PSince the half-life of T4 is about two weeks, your adaptations to it have just begun, but your TSH would already be significantly lowered by it. After you have been on a certain dose for at least two weeks, the blood tests would be easier to interpret. Did the supplement affect the night sweats?

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Ray Peat said:

Pregnenolone does convert to either DHEA or progesterone. Sugar and brewer's yeast are other things that help with the regeneration. Keeping free fatty acids low is important, and niacinamide could help with that.

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Ray Peat said:

I suspect that it will age the skin. Have you tried topical sulfur and oral tetracycline?

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Ray Peat said:

Antibiotics generally shouldn't be used during pregnancy. Sulfur (precipitated or sublimed) can be mixed into a slurry with water and patted onto the area. Dissolved aspirin used with it increases the antiseptic effect and reduces inflammation.

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Ray Peat said:

The people who wrote the label should be removed to fresh air immediately, their brains aren't getting enough oxygen. There are forms of sulfur that are ground, rather than precipitated, and they aren't as effective, but they aren't harmful. If it has a very strong smell, it might be contaminated; the smell should be mildly unpleasant. Ground sulfur/brimstone is commonly used in animal feed, so it isn't toxic.

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Ray Peat said:

Yes, the smell varies slightly. When there's a skin fungal infection, there's a hydrogen sulfide stink, which is what kills the fungus.E

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Ray Peat said:

If you wake up feeling refreshed, I think it's very good to now and then get some extra sleep. Under-sleeping increases nitric oxide, and catch-up sleep lowers it. Niacinamide, coffee, and aspirin are things that lower NO.

DNA Cell Biol. 2014 Aug 5. [Epub ahead of print]
Apoptosis of Beta Cells in Diabetes Mellitus.
Anuradha R(1), Saraswati M, Kumar KG, Rani SH.
(1)Department of Genetics, Osmania University , Hyderabad, India .
Diabetes mellitus is a multifactorial metabolic disorder characterized by
hyperglycemia. Apoptosis in beta cells has been observed in response to diverse
stimuli, such as glucose, cytokines, free fatty acids, leptin, and sulfonylureas,
leading to the activation of polyol, hexosamine, and diacylglycerol/protein
kinase-C (DAG/PKC) pathways that mediate oxidative and nitrosative stress causing
the release of different cytokines. Cytokines induce the expression of Fas and
tumor necrosis factor-alpha (TNF-α) by activating the transcription factor,
nuclear factor-κb, and signal transducer and activator of transcription 1
(STAT-1) in the β cells in the extrinsic pathway of apoptosis. Cytokines produced
in beta cells also induce proapoptotic members of the intrinsic pathway of
apoptosis. The genetic alterations in apoptosis signaling machinery and the
pathogenesis of diabetes include Fas, FasL, Akt, caspases, calpain-10, and
phosphatase and tensin homolog (Pten). The other gene products that are involved
in diabetes are nitric oxide synthase-2 (NOS2), small ubiquitin-like modifier
(SUMO), apolipoprotein CIII (ApoCIII), forkhead box protein O1 (FOXO1), and
Kruppel-like zinc finger protein Gli-similar 3 (GLIS3). The gene products having
antiapoptotic nature are Bcl-2 and Bcl-XL. Epigenetic mechanisms play an
important role in type I and type II diabetes. Further studies on the apoptotic
genes and gene products in diabetics may be helpful in pharmacogenomics and
individualized treatment along with antioxidants targeting apoptosis in diabetes.

Autoimmunity. 1994;19(3):193-8.
Nicotinamide decreases nitric oxide production and partially protects human
pancreatic islets against the suppressive effects of combinations of cytokines.
Eizirik DL(1), Sandler S, Welsh N, Bendtzen K, Hellerström C.
(1)Department of Medical Cell Biology, Uppsala University, Sweden.
It has been recently reported that human pancreatic islets in tissue culture
produce nitric oxide (NO) and show a decreased function when exposed for 6 days
to combinations of cytokines (interleukin-1 beta (IL-1 beta) + tumor necrosis
factor-alpha (TNF-alpha) + interferon-gamma (IFN-gamma). Here we study the
effects of nicotinamide (Nic; 10 or 20 mmol/l) on these deleterious effects of
cytokines (50 U/ml IL-1 beta + 1000 U/ml TNF-alpha + 1000 U/ml IFN-gamma). Islets
were isolated from 8 human pancreata at the Central Unit of the beta-Cell
Transplant, Brussels, sent to Uppsala and, after 3-5 days in culture, exposed for
6 additional days to the cytokines and/or Nic. The cytokines induced a 6-fold
increase in islet NO production (P < 0.001), and this effect was partially
counteracted by Nic (50-60% decrease in NO production; P < 0.001). The cytokines
severely decreased the islet insulin content and glucose-induced insulin release
(16.7 mmol/l glucose; 90% decrease; P < 0.001). Both these effects of cytokines
were partially counteracted by Nic, especially at the highest concentration (20
mmol/l; 2-4-fold increase compared to islets exposed to cytokines alone; P <
0.01). Nic by itself did not affect the insulin content or insulin release by
control islets. In conclusion, the present data indicate that Nic counteracts the
deleterious effects of cytokines on human pancreatic islets. This effect of Nic
may be relevant for the beneficial effects of the drug in early IDDM.

Vitam Horm. 2014;95:299-322.
β-cell responses to nitric oxide.
Broniowska KA(1), Oleson BJ(1), Corbett JA(2).
(1)Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin,
USA.
(2)Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin,
USA. Electronic address: [email protected].
Autoimmune diabetes is characterized by the selective destruction of
insulin-secreting β-cells that occurs during an inflammatory reaction in and
around pancreatic islets of Langerhans. Cytokines such as interleukin-1, released
by activated immune cells, have been shown to inhibit insulin secretion from
pancreatic β-cells and cause islet destruction. In response to cytokines, β-cells
express inducible nitric oxide synthase and produce micromolar levels of the free
radical nitric oxide. Nitric oxide inhibits the mitochondrial oxidation of
glucose resulting in an impairment of insulin secretion. Nitric oxide is also
responsible for cytokine-mediated DNA damage in β-cells. While nitric oxide
mediates the inhibitory and toxic effects of cytokines, it also activates
protective pathways that allow β-cells to recover from this damage. This review
will focus on the dual role of nitric oxide as a mediator of cytokine-induced
damage and the activator of repair mechanisms that protect β-cells from
cytokine-mediated injury.
© 2014 Elsevier Inc. All rights reserved.

Diabetes. 1992 Aug;41(8):897-903.
Does nitric oxide mediate autoimmune destruction of beta-cells? Possible
therapeutic interventions in IDDM.
Corbett JA(1), McDaniel ML.
(1)Department of Pathology, Washington University School of Medicine, Saint Louis,
Missouri 63110.
Cytokines have been implicated as immunological effector molecules that induce
dysfunction and destruction of the pancreatic beta-cell. The mechanisms of
cytokine action on the beta-cell are unknown; however, nitric oxide, resulting
from cytokine-induced expression of nitric oxide synthase, has been implicated as
the cellular effector molecule mediating beta-cell dysfunction. Nitric oxide is a
free radical that targets intracellular iron-containing enzymes, which results in
the loss of their function. The cytokine IL-1 beta induces the formation of
nitric oxide in isolated rat islets and the insulinoma cell line, Rin-m5F. NMMA
and NAME, both inhibitors of nitric oxide synthase, completely protect islets
from the deleterious effects of IL-1 beta. These inhibitors are competitive in
nature and inhibit both the cytokine-inducible and constitutive isoforms of
nitric oxide synthase with nearly identical kinetics. This may preclude their use
as therapeutic agents because of increases in blood pressure which result from
the inhibition of constitutive nitric oxide synthase activity. Aminoguanidine, an
inhibitor of nonenzymatic glycosylation of cellular and extracellular
constituents associated with diabetic complications, recently has been reported
to inhibit nitric oxide synthase. Aminoguanidine is approximately 40-fold more
effective in inhibiting the inducible isoform of nitric oxide synthase,
suggesting that aminoguanidine or analogues may serve as potential therapeutic
agents to block diseases associated with nitric oxide production by the inducible
isoform of nitric oxide synthase. In vivo administration of TNF IL-1 has been
shown to induce anti-diabetogenic effects in the NOD mouse. This
anti-diabetogenic effect of cytokines appears to conflict with evidence
suggesting that cytokines mediate beta-cell dysfunction.(ABSTRACT TRUNCATED AT
250 WORDS)

Biochemistry. 1993 Dec 21;32(50):13767-70.
IL-1 beta induces the coexpression of both nitric oxide synthase and
cyclooxygenase by islets of Langerhans: activation of cyclooxygenase by nitric
oxide.
Corbett JA(1), Kwon G, Turk J, McDaniel ML.
(1)Department of Pathology, Washington University School of Medicine, St. Louis,
Missouri 63110.
Autoimmune diabetes is characterized by an early infiltration of lymphocytes into
and around islets, which is followed by selective destruction of the
insulin-secreting beta-cell. Cytokines released during this inflammatory reaction
have been implicated as effector molecules which mediate beta-cell destruction.
In vitro treatment of rat islets with the cytokine IL-1 beta results in an
inhibition of glucose-stimulated insulin secretion that is mediated by the
overproduction of nitric oxide. IL-1 beta also stimulates the production of the
cyclooxygenase (COX) product prostaglandin E2 (PGE2). In this study we have
examined the effects of IL-1 beta on both inducible nitric oxide synthase (iNOS)
and inducible cyclooxygenase (iCOX) expression, and the direct effects of nitric
oxide on the activity of COX. Treatment of rat islets with 5 units/mL IL-1 beta
induces a similar time-dependent production of both nitrite and PGE2. IL-1
beta-induced nitrite and PGE2 production is attenuated by the NOS inhibitor
NG-monomethyl-L-arginine (NMMA), but NMMA has no inhibitory effect on the
expression of either iCOX or iNOS as determined by immunoprecipitation.
Actinomycin D prevents IL-1 beta-induced iCOX and iNOS expression and the
production of both nitrite and PGE2 by islets, suggesting that mRNA transcription
is required for IL-1 beta-induced expression of both iNOS and iCOX. The effects
of exogenous arachidonic acid on both constitutive COX (cCOX) and iCOX activity
were also investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrinology. 1993 Oct;133(4):1739-43.
Nicotinamide and dexamethasone inhibit interleukin-1-induced nitric oxide
production by RINm5F cells without decreasing messenger ribonucleic acid
expression for nitric oxide synthase.
Cetkovic-Cvrlje M(1), Sandler S, Eizirik DL.
Author information:
(1)Department of Medical Cell Biology, Uppsala University, Sweden.
Nitric oxide (NO) generation may be a final common pathway for beta-cell damage
in early insulin-dependent diabetes mellitus. Insulin-producing cells express an
inducible form of NO synthase (iNOS), which is similar to that observed in
activated macrophages. Induction of iNOS mRNA in these cells depends on protein
synthesis. To further characterize the regulation of iNOS induction in
insulin-producing cells, RINm5F cells (RIN cells) were exposed for 6 h to human
recombinant interleukin-1 beta (rIL-1 beta; 1 ng/ml) alone or in combination with
either nicotinamide (10, 20, or 50 mM) or dexamethasone (1 or 5 microM). These
agents have been previously shown to prevent activation of iNOS in macrophages,
fibroblasts, and hepatocytes. rIL-1 beta induced the expression of iNOS mRNA in
RIN cells and a 12- to 13-fold increase in medium nitrite accumulation, the
latter indicating NO production. Nicotinamide decreased nitrite production in a
dose-dependent way. Thus, 10 mM nicotinamide decreased rIL-1 beta-induced nitrite
formation by 30%, 20 mM by 60%, and 50 mM by 90%. The highest concentration of
nicotinamide also prevented rIL-1 beta-induced iNOS mRNA, an effect associated
with inhibition of total protein biosynthesis. However, 10 or 20 mM nicotinamide
did not modify rIL-1 beta-induced iNOS mRNA expression or inhibit protein
biosynthesis. Dexamethasone also decreased rIL-1 beta-induced nitrite production
without affecting iNOS mRNA expression. As a whole, these data suggest that both
nicotinamide and dexamethasone may prevent NO accumulation in insulin-producing
cells by posttranscriptional mechanisms. It is also possible that these drugs
induce direct inhibition of iNOS enzymatic activity and/or scavenge NO. Higher
concentrations of nicotinamide might also inhibit iNOS mRNA expression, possibly
by blocking protein biosynthesis.

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Ray Peat said:

Endoscopy and biopsy can identify it, blood tests are often not reliable. Home made, slowly leavened bread contains much less gluten than the instantly leavened bread most bakeries sell.

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Ray Peat said:

Diabetes tends to interfere with the activity of thyroid hormone, and low thyroid function is closely connected to gall bladder problems. It's important to have some carbohydrate with protein foods, to prevent decreased blood sugar symptoms.

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Ray Peat said:

No.

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Ray Peat said:

Aspirin helps to increase the oxidation of glucose, reinforcing the effects of thyroid hormone. It can antagonize vitamin K, potentially increasing a bleeding tendency, but with a supplement of K it's safe to test the effects of a standard 5 grain tablet with a meal twice a day, to see if it helps to prevent hyperglycemia. The cynoplus should start with a sixth of a tablet per day, watching for effects during the first two weeks. Too much could raise blood sugar rather than regulating it; I hope no one is suggesting beginning with a whole tablet per day. The appropriate amount of progesterone depends on the need and time of month. Vitamin B1 helps to oxidize glucose, so its use should be adjusted according to need.

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Ray Peat said:

Zinc* isn't directly an oxidant, but when it's used as a chemical supplement it can cause problems that it wouldn't in the form of foods. Both vitamin A and zinc are essential in the right amount for good skin health, but too much of either can disturb the immune function. Irritation of the intestine is often involved in skin problems, and supplements always contain trace contaminants that can cause reactions. When ADM bought Distillation Products from Eastman several years ago, the composition of their vitatmin E products went through several changes, and competing companies began making similar changes. Since then research results haven't been as consistent as they were 40 to 60 years ago, and I stopped recommending amounts up to a few hundred units per day, waiting to see more results of research. Some of the products sold as vitamin E now contain significant amounts of PUFA, and lack some of the substances such as octacosanol that were in traditional products. The right amount of thyroid is essential for skin immunity and metabolism of steroids in the skin. Topical anti inflammatory things such as tetracycline and aspirin often produce the quickest response.

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Ray Peat said:

Antibiotics can be used topically, but the tetracycline type is usually taken internally, for their antiinflammatory effect. Changing the diet while using an antibiotic can make the effect permanent.

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