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Saturday, 9 July 2016

This little piggy had none: are fat soluble micronutrients diluted by serum lipids in CVD and psoriasis?

This will be a rambling post, I'm afraid, and more of a sketch of an idea rather than a pinning down.

This excellent pig study, first tweeted by Prof Andro of the Suppversity blog, is clear proof that the Seven Countries study, as long suspected, was severely confounded by latitude, sunlight exposure, and vitamin D.Summary

4 groups of swine (n=16) fed 2 different atherogenic diets, one with 1500iu vs 500iu vit D3, the other with 1,300iu vs no vit D (calcium was supplemented when level dropped too much). for 12 months.
Diet was (as far as I can tell) high sugar (30-50%), high saturated fat (~40% cocoa butter and ghee), with added cholesterol and cholate, plus 8% and 9% chocolate (sic).
Difference between the 2 diets was vitamin D, and may also have been refined versus semi-refined.
Swine fed diet 1 plus 500iu D3 had marked atherosclerosis, swine fed diet 1 plus 1,500iu had very mild changes. Swine fed diet 2 plus zero vit D3 had severe atherosclerosis, swine fed diet 2 plus 1,300iu D3, well this little piggy had none.

(image borrowed from Fat Emperor blog of Ivor Cummings)
The higher the serum cholesterol, the healthier the arteries. Healthiest swine had cholesterol of 406 +/- 34.8 mg/dL, sickest of 352 +/- 33.8 mg/dL, on same atherogenic diet 2.
As a footnote, the rodent version of this company's atherogenic diet (high sugar, high SFA) has "will not cause obesity" on its webpage. Of course not - it would need to supply more PUFA for that to happen.

Anyway, here we have 1,300-1,500iu of vitamin D3 preventing atherosclerosis in pigs (a reasonably human-compatible model, as anyone who's used porcine insulin will attest) weighing 47-57 Kg, making an equivalent human dose a little higher. To get this much vitamin D3 without supplements you'd need to eat lots of salmon (at least 300g/day) or get some sun.

I get psoriasis in winter, just a touch, a few cm but not nice to be itchy. It fades and heals in the summer. I looked up whether it was related to my high cholesterol and it is, it has its own cholesterol pathology and correlation with CVD (but only significant if it covers a larger area than I get).

Recently I decided to supplement vit D3 again - it's midwinter here. I took 10,000iu week on, week off, to get my levels up. After the first week I noticed my psoriasis had stopped itching and was healing. Now I take 6,000iu/day and it's still good.

I found this study using a whopping 35,000iu/day long term for psoriasis and vitiligo.

Dermatoendocrinol. 2013 Jan 1; 5(1): 222–234.
A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis
Danilo C Finamor, Rita Sinigaglia-Coimbra, Luiz C. M. Neves, Marcia Gutierrez, Jeferson J. Silva, Lucas D. Torres, Fernanda Surano, Domingos J. Neto, Neil F. Novo, Yara Juliano, Antonio C. Lopes, and Cicero Galli Coimbra.

Great stuff - fortune favours the brave, and this worked. To tolerate such a high dose of D3, the participants had to restrict dietary calcium. (avoiding dairy products and calcium-enriched foods like oat, rice or soya “milk”) and drink at least 2.5L of fluid per day. Remember, the vitamin D deficient pigs needed to have calcium supplemented after 6 months.

The PASI score significantly improved in all nine patients with psoriasis. Fourteen of 16 patients with vitiligo had 25–75% repigmentation. Serum urea, creatinine and calcium (total and ionized) did not change and urinary calcium excretion increased within the normal range. High-dose vitamin D3 therapy may be effective and safe for vitiligo and psoriasis patients.

So why were such high doses of D3 needed? Fat soluble vitamins are carried to cells on lipid particles, especially LDL, as noted by Doll and Petit in The Causes of Cancer, 1981.

Maret Traber of the Linus Pauling Institute has recently found that high levels of cholesterol and triglycerides reduce the availability of vitamin E to cells.

" In the continuing debate over how much vitamin E is enough, a new study has found that high levels of blood lipids such as cholesterol and triglycerides can keep this essential micronutrient tied up in the blood stream, and prevent vitamin E from reaching the tissues that need it.

The research, just published in the American Journal of Clinical Nutrition, also suggested that measuring only blood levels may offer a distorted picture of whether or not a person has adequate amounts of this vitamin, and that past methods of estimating tissue levels are flawed.

The findings are significant, the scientists say, because more than 90 percent of the people in the United States who don’t take supplements lack the recommended amount of vitamin E in their diet.

Vitamin E is especially important in some places such as artery walls, the brain, liver, eyes and skin, but is essential in just about every tissue in the body. A powerful, fat-soluble antioxidant, it plays important roles in scavenging free radicals and neurologic function. In the diet, it’s most commonly obtained from cooking oils and some vegetables."

And there you have the big confounder in studies that suggest that PUFAs from vegetable oils reduce the risk of CVD and other diseases (including neurological causes of death in the recent NHS and HPFS update). These oils are major sources of vitamin E, but so are nuts, and nuts are associated with the same protection, except better, in relatively small amounts.

This research raises particular concern about people who are obese or have metabolic syndrome,” said Traber, who is the Helen P. Rumbel Professor for Micronutrient Research in the College of Public Health and Human Sciences at Oregon State University, and a principal investigator in OSU’s Linus Pauling Institute.

“People with elevated lipids in their blood plasma are facing increased inflammation as a result,” Traber said. “Almost every tissue in their body is under oxidative attack, and needs more vitamin E. But the vitamin E needed to protect these tissues is stuck on the freeway, in the circulatory system. It’s going round and round instead of getting to the tissues where it’s needed.”

This research was done with 41 men and women, including both younger and older adults, who obtained vitamin E by eating deuterium-labeled collard greens, so the nutrient could be tracked as it moved through the body. Of some interest, it did not find a significant difference in absorption based solely on age or gender. But there was a marked difference in how long vitamin E stayed in blood serum, based on higher level of lipids in the blood – a more common problem as many people age or gain weight."
From an earlier review of vitamin E metabolism and function, by Brigelius-Flohé and Traber:

Similarly, vitamin E deficiency anemia occurs, largely in premature infants, as a result of free radical damage (47). Diminished erythrocyte life span (48, 49) and increased susceptibility to peroxide-induced hemolysis are apparent not only in severe deficiency, but also in marginal vitamin E deficiency in
hypercholesterolemic subjects (50).
Ref 50 is 
Simon, E., Paul, J. L., Atger, V., Simon, A., and Moatti, N.
(1998) Erythrocyte antioxidant status in asymptomatic hypercholesterolemic men. Atherosclerosis 138, 375–381

I have rambled quite long enough. Look beyond the antioxidant focus of what Maret Traber says; fat soluble vitamins and antioxidants are also modifiers of inflammatory responses, endothelial function, and clotting cascades. We know that lipids are sometimes raised by factors that also cause inflammation independently, and that high cholesterol can often be found together with longevity.

If Traber's findings apply to the other fat-soluble vitamins and antioxidants as well, then we have an explanation for the inconsistencies in the relationship between LDL and the risk of CVD and other diseases. In particular, if LDL is elevated by a diet supplying more of these nutrients, it is likely to be healthier than the elevation of triglycerides and perhaps LDL by a diet that doesn't supply as many; a grain-based, refined sugar, low fat diet. Thus the nutrient density of fatty foods and the vegetables consumed with them becomes important. And so does the sun, and our ability to find vitamin D3 in winter.