Vitamin C

As the various brands of Paleo out there seem to slowly mutate over time, they are seeming to become closer and closer approximations of Paul Jaminet's Perfect Health Diet. While this isn't proof that he is correct about everything, I do take it as evidence in his favor.

There are several interesting posts on the site about Vitamin C, such as:

NZ Man Left for Dead by Doctors, Cured by Vitamin C
http://perfecthealthdiet.com/2010/08/nz-man-left-for-dead-by-doctors-cured-by-vitamin-c/

[V]itamin C supports respiratory bursts by recycling glutathione and providing antioxidant protection for leukocytes against their own respiratory bursts, and also supports anti-viral immunity [...]

Vitamin C vs modern medicine
http://perfecthealthdiet.com/2010/09/vitamin-c-vs-modern-medicine/

Fighting Viral Infections by Vitamin C at Bowel Tolerance
http://perfecthealthdiet.com/2010/09/fighting-viral-infections-by-vitamin-c-at-bowel-tolerance/

A well-tested therapeutic strategy would be to take 4 g vitamin C every hour with water until bowel intolerance is reached. The therapy is extremely safe, and its effectiveness is usually apparent within days.

Danger of Zero-Carb Diets III: Scurvy
http://perfecthealthdiet.com/2010/11/danger-of-zero-carb-diets-iii-scurvy/

There is no direct transport of vitamin C into the brain, yet the brain is one of the most vitamin C-dependent tissues in the body. The brain relies entirely on GLUT1-mediated transport of DHAA from the blood for its vitamin C supply. Within the brain, DHAA is restored to vitamin C by glutathione. Supplying DHAA to stroke victims (of the mouse persuasion) as late as 3 hours after the stroke can reduce the stroke-damaged volume by up to 95%

Vitamin C: Should you take it before and after surgery? Part 1
http://perfecthealthdiet.com/2014/04/vitamin-c-surgery-part-1/

[V]itamin C can help normalize pain-inhibiting pathways involving dopamine, NMDA, and other neurotransmitters, and has shown promise for a variety of pain conditions in animal models. A higher vitamin C dose of 2 grams was shown to reduce morphine use after surgery.

If grandma or grandpa is hospitalized with a respiratory infection, remember that vitamin C significantly improves respiratory function in these patients.

Finally, if you fracture your wrist, that is one instance where taking vitamin C (500 mg/d for 50 days) is unequivocally and officially recommended by evidence-based guidelines.

Vitamin C: Should you take it before and after surgery? Part 2
http://perfecthealthdiet.com/2014/04/vitamin-c-take-surgery-part-2/


I imagine the more one digs, the more one finds about Vitamin C.

This headline caught my eye this morning:

Low Vitamin C Linked to Intracerebral Hemorrhage
http://www.medscape.com/viewarticle/820660 (may require sign in)

"This link is probably associated with the role of vitamin C in blood pressure regulation and collagen biosynthesis," although other factors may also play a role, said Dr. Vannier.

This makes one wonder if patients on Anticoagulant therapy like Warfarin should be routinely supplementing Vitamin C, or at the very least, have their levels checked:

What causes intracerebral hemorrhage during warfarin therapy?
http://www.neurology.org/content/55/7/907

 It is a cruel irony that the use of warfarin, given to prevent ischemic stroke, increases the risk of severe hemorrhagic stroke as its most devastating complication. Conventional intensities of anticoagulation increase the risk of intracerebral hemorrhage 5 to 10 times, by absolute rates of 1% per year or more for many stroke-prone patients. The increased intracerebral bleeding associated with warfarin therapy offsets its benefits in certain patient populations.

I was glad to see that several of the foods I eat regularly are good sources of Vitamin C:

1 cup of Bell Peppers has 117 mg
1 cup of Broccoli has 101 mg
1 cup of Brussels sprouts has 97 mg
1 cup of Cauliflower has 55 mg
1 cup of Cabbage has 52 mg
1 cup of Tomatoes has 25 mg
1 cup of Spinach has 18 mg
1 medium-sized Sweet potato has 39 mg

Compare these to the "gold standard", 1 medium-sized Orange, which contains 70 mg

Recent rambling investigations

I spent some time recently investigating Vitamin K2 & Osteocalcin.

1st, there are apparently 2 forms of Osteocalcin -- undercarboxylated Osteocalcin (ucOC) & gamma-carboxylated Osteocalcin. Which one is good? Which one is bad? What do we want? It gets complicated.

At 1st glance, it looks like ucOC is good:

Change in Undercarboxylated Osteocalcin Is Associated with Changes in Body Weight, Fat Mass, and Adiponectin: Parathyroid Hormone (1-84) or Alendronate Therapy in Postmenopausal Women with Osteoporosis (the PaTH Study)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232610/

I keep forgetting to always keep in mind which population the study was conducted in. I'm not a post-menopausal woman with Osteoporosis, so the findings of this might not apply to me well or at all.

Anyway, in short they found:

↑ ucOC --> ↑ Adiponectin; ↓ Body weight & ↓ Fat

In the study women given PTH (Parathyroid hormone) saw increased levels of ucOC & women given Bisphosphonates saw decreased ucOC. This was interesting to me since a lot of patients take Bisphosphonates & I was unaware of the potential negative effects on body composition they might have.

Moving on, here's another study that makes ucOC look good:

Undercarboxylated osteocalcin is positively associated with free testosterone in male patients with type 2 diabetes mellitus.

https://www.ncbi.nlm.nih.gov/pubmed/22669468

Again, mind the population. I don't have T2DM (Type 2 diabetes mellitus) & I hope I never will.

Anyway:

↑ ucOC --> ↑ Free testosterone (note: this is not a causal relationship, just an association)

So far this sounds quite good from a body composition standpoint. Who doesn't want to lose weight, lose fat, & increase free testosterone?

The bad news came in this study:

Vitamin K supplementation reduces serum concentrations of under-γ-carboxylated osteocalcin in healthy young and elderly adults

http://ajcn.nutrition.org/content/72/6/1523.long

Here the authors write:

↑ ucOC --> ↑ Fracture risk;  ↓ BMD (Bone mineral density) (note: also an association)

They knew that there is an association between Vitamin K insufficiency & elevated ucOC:

 ↓ VitK --> ↑ ucOC

They wanted to see if supplementing Vitamin K (in this case K1 AKA Phylloquinone) would lower ucOC levels & it did. The idea here being:

 ↑ VitK --> ↓ ucOC --> ↓ Fracture risk; ↑ BMD

So it seems ucOC is not clear-cut. We may want higher levels from a body composition standpoint, but lower levels from a bone health standpoint. I'm a young male, so you might think bone health should be low on my list of priorities, but I came across an interesting fact the other day that up to 25% of men will suffer a Fracture due to Osteoporosis during their lifetime -- 1 in 4, not terribly good odds.

Keeping with the beneficial effects of Vitamin K on bone health, I found this:

Treatment with vitamin D3 and/or vitamin K2 for postmenopausal osteoporosis.

https://www.ncbi.nlm.nih.gov/pubmed/14529146

The authors state:

[T]reatment with 1alpha-hydroxyvitamin D3 (alfacalcidol) slightly reduces bone turnover, sustains lumbar bone mineral density (BMD), and prevents osteoporotic vertebral fractures in postmenopausal women with osteoporosis, while vitamin K2 (menatetrenone) enhances gamma-carboxylation of bone glutamic acid residues and secretion of osteocalcin, sustains lumbar BMD, and prevents osteoporotic fractures in patients with osteoporosis.

 They go on:

Available evidence suggests that the effect of vitamin K2 on mineralization by human periosteal osteoblasts is enhanced in the presence of 1,25 dihydroxyvitamin D3 in vitro. The effect of vitamin K2 on BMD in ovariectomized rats is affected by the plasma 25-hydroxyvitamin D3 level in vivo, and is significant only when rats are fed a diet containing vitamin D3. Based on this line of evidence, combined treatment with alfacalcidol and menatetrenone for osteoporosis is surmised to be more effective than treatment with menatetrenone alone, and may have anabolic effects on osteoporotic bone.

In short, Vitamin D3 & Vitamin K2 are both good for bone health & potentiate the effects of one another.

One last pro-bone health study, just to be thorough:

Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women.

https://www.ncbi.nlm.nih.gov/pubmed/17287908

This study was interesting to me because it pointed out the difference between BMD (Bone mineral density) & BMC (Bone mineral content). Looking at BMD alone may not provide enough information because:

Unlike BMC, DXA-BMD does not take into account the geometry (size, thickness) of bone, which has an independent [positive] contribution to bone strength and fracture risk. 

In conclusion, although I am not a post-menopausal woman with Osteoporosis, bone health does sound appealing to me & I believe there are other benefits to supplementing Vitamin K2 as well. Plus, I love natto (纳豆). While Vitamin K2 might decrease ucOC levels which might have negative effects on body composition, I am not too sure about the strength of this correlation & where it stands compared to other factors such as overall diet, activity level, etc. I imagine the effect is not too large since my body composition is quite good despite regular intake of large amounts of this delicious fermented food product.

Intermittent fasting

Improvements in coronary heart disease risk indicators by alternate-day fasting involve adipose tissue modulations.

http://www.ncbi.nlm.nih.gov/pubmed/20300080
16 obese subjects instituted an alternate-day fasting program (eat for 24 hours, then fast for 24 hours). Subjects lost Body weight (average loss: 5.7 +/- 0.9 kg) but not Lean body mass. They had lower LDL cholesterol levels & reduced Waist circumference.

Alternate-day fasting and chronic disease prevention: a review of human and animal trials.

www.ncbi.nlm.nih.gov/pubmed/17616757
Human trials support beneficial effects on HDL & Triglycerides. Animal studies support beneficial effects on Diabetes incidence, Cancer, fasting Blood glucose, Insulin concentrations, Total cholesterol, Blood pressure, & response to Myocardial infarction (Heart attack).

Lying & Health

The study is not yet peer reviewed or published, but the headline caught my eye:

Study finds that avoiding lies can improve your health
http://www.usatoday.com/news/health/story/2012-08-04/honesty-beneficial-to-health/56782648/1?csp=34news - 1 group was instructed not to lie, the other served as the control. Researchers found that decreased lying was associated with better mental & physical health. Participants also reported that their social interactions went more smoothly.

... when participants in the no-lie group told three fewer white lies than they did in other weeks, they experienced, on average, approximately four fewer mental-health complaints and about three fewer physical complaints.

Personally, I seldom lie. If I do find myself wanting to lie, it prompts me to ask myself some questions. Why do I want to lie? Am I ashamed of what I'm doing? Am I trying to avoid some kind of conflict? If I am ashamed of what I'm doing, why am I doing it? Or maybe, how can I hide it better so that I don't feel the need to lie about it in the future? Why avoid conflict? Maybe conflict is the better option. Maybe through conflict I can test my beliefs & convictions or even convince the other party of something.

An example that comes to mind is lying about my eating habits. My wife's mother is always trying to get me to eat Fruit, but my currently favored hypothesis is that Fruit is not good for you. Rather than arguing with her & having her disappointed or frustrated, it might be easier to just take the Fruit & give it to someone at work or throw it away when I'm out of her sight.

Perhaps trying not to offend her is harmful, though. Maybe what I should do is to convince her. Sort of like yanking out a bad tooth, a brief, painful conflict will prevent greater amounts of stress & strife down the line.

LDL & Mortality

So I stumbled on this interesting bit today & it got me researching:

This is in reference to Primary prevention (i.e. trying to reduce the risk of Cardiovascular disease in patients that don't have it yet). The Party Line is that Cholesterol is evil & lowering Cholesterol will save lives. So if a patient doesn't tolerate a Statin, why not just put them on some other drug that lowers Cholesterol? Any drug that lowers Cholesterol should save lives, shouldn't it?

Well, no.

As it turns out, there are a slew of studies showing that various other Cholesterol lowering drugs have either Neutral or Harmful effects:

Clofibrate lowered Cholesterol, but increased Mortality
http://www.ncbi.nlm.nih.gov/pubmed?term=6105515 - Lancet 1980

“Explanation of the excess mortality is not apparent: a long term toxic effect of clofibrate, the possible consequences of reducing body cholesterol pools and, remotely, chance have all to be considered.” [emphasis mine]

Cholestyramine reduced Total cholesterol & LDL, but had no effect on All-cause mortality
http://www.ncbi.nlm.nih.gov/pubmed?term=6361300  - JAMA 1984

Clofibrate reduced Cholesterol by 9% but increased All-cause mortality (77 deaths vs. 47 deaths, P less than 0 .01)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC483536/pdf/brheartj00224-0001.pdf - Br Heart J 1978

Gemfibrozil reduced Total cholesterol, LDL, Non-HDL cholesterol, & Triglycerides, but had no effect on All-cause mortality
http://www.ncbi.nlm.nih.gov/pubmed?term=3313041 - Frick MH in N Engl J Med 1987

So apparently none of these Non-statin interventions save lives, so they aren't recommended.

What about Statins themselves?

Boom:

Meta-analysis: Statins have no effect on All-cause mortality
http://www.ncbi.nlm.nih.gov/pubmed?term=20585067 - Ray KK in Arch Intern Med 2010

Okay, okay. So we have pretty strong evidence that lowering LDL doesn't save lives, but lowering LDL prevents Cardiovascular events, so THAT is why we need to get everyone scared of Cholesterol.

Actually, no.

Pravastatin reduced CHD (Coronary heart disease) but did not reduce All-cause mortality; reduced CHD was NOT correlated with LDL reduction
http://www.ncbi.nlm.nih.gov/pubmed?term=9576423 - WOSCOPS trial in Circulation 1998

Did you get that? The reduction in CHD caused by Pravastatin was independent of LDL.

Here's another one:

Analysis of AFCAPS/TexCAPS data: Lovastatin prevented CHD in subjects with low Total:HDL ratios AND high CRP levels, but did not in subjects with low Total:HDL ratios and LOW CRP levels
http://www.ncbi.nlm.nih.gov/pubmed?term=11430324 - Ridker PM in N Engl J Med 2001


This seems to suggest that the reduction in CHD caused by Statins might be due to some kind of Anti-inflammatory effect, NOT due to effects on Cholesterol.

The next study didn't look at CHD or Mortality, but looked at Carotid-artery intima thickness (CIMT):

Simvastatin plus Ezetimibe lowers LDL more than Simvastatin alone, but has no greater effect on CIMT than Simvastatin alone
www.ncbi.nlm.nih.gov/pubmed/18376000 - Kastelein JJ in N Engl J Med 2008

In this study average LDL was 192.7 in the Simvastatin-only group & 141.3 in the Simvastatin-plus-Ezetimibe group. If lowering LDL is what improves Carotid-artery disease, why doesn't lowering LDL another 51 points give us any improvement?

To summarize:

• Non-statin Lipid-lowering drugs aren't recommended for Primary prevention because they don't reduce All-cause mortality.
• Statin drugs for Primary prevention don't reduce All-cause mortality.
• Statin drugs DO reduce some forms of CVD, but this effect seems to be independent of their effects on LDL.

Fructose, Metabolic syndrome, & Fatty liver

Fructose induces Metabolic syndrome via increasing Uric acid in Rats
http://www.ncbi.nlm.nih.gov/pubmed/16234313 - Researchers performed several experiments. 1st, they saw that Fructose feeding induces Hyperinsulinemia, Hypertriglyceridemia, & Hyperuricemia. 2nd, they gave Fructose-fed Rats drugs to lower Uric acid levels & found that these drugs prevented or reversed the symptoms of Metabolic syndrome. Finally, they showed that Uric acid inhibits Endothelial function in a dose-dependent fashion.

Consumption of Fructose-sweetened drinks induces Metabolic syndrome in Humans
http://www.ncbi.nlm.nih.gov/pubmed/22828276 - 32 subjects were divided into 2 groups, with 1 receiving 25% of their calories from a Fructose-sweetened beverage & the other from a Glucose-sweetened beverage. The group who consumed the Fructose-sweetened beverages had significantly elevated levels of Uric acid, RBP4 (Retinol-binding protein 4, associated with Insulin resistance), & GGT (Gamma-glutamyl transferase or transpeptidase, also associated with Metabolic syndrome and/or Non-alcoholic fatty liver disease [NAFLD]).

Fructose causes Dyslipidemia & Fat deposition in the Liver & Muscle in Healthy Humans
http://www.ncbi.nlm.nih.gov/pubmed/19403641 - 24 subjects were given either an isocaloric diet or hypercaloric Fructose diet for 7 days. The Fructose diet caused an increase in Fat in the Liver, Fat in the Muscle, VLDL (sometimes referred to as "very bad" Cholesterol), & fasting hepatic glucose output. Some of the patients were children of people with Diabetes, and in this subgroup, the effects of Fructose were worse.

Vitamin D, Testosterone, & Coffee

Vitamin D increases Testosterone levels
http://www.ncbi.nlm.nih.gov/pubmed/21154195 - 54 overweight, non-diabetic men with deficient Vitamin D levels (<50 nmol/L) undergoing a weight reduction program were randomized to ~3000IU Vitamin D daily for 1 year or Placebo. Vitamin D levels increased by ~50 nmol/L & Total testosterone levels increased by ~11 to 13 nmol/L in the Treatment group, with no change seen in the Placebo group.

For reference, hormone therapy is usually started for men with Total testosterone < ~12 nmol/L.

Testosterone improves Metabolic syndrome
http://www.medscape.com/viewarticle/755673 -147 men with Total testosterone levels <~12 nmol/L were given 1000 mg Testosterone undecanoate injections every 3 months for at least 4 years. The average waist reduction was 8 cm; average weight loss was 12.9 kg. During the 1st year of treatment the average Lean body mass increase was 4.5 - 5 kg & average Fat loss was 5 to 6 kg. Total cholesterol, LDL, & Triglycerides were all significantly reduced; C-reactive protein levels (a marker of Inflammation) dropped from 7.1 to 1.6 mg/L.

Testosterone aids Weight loss & Waist-size reduction
http://www.medscape.com/viewarticle/767696 -130 men with Total testosterone levels <~12 nmol/L were given 1000mg Testosterone undecanoate injections on Day 1, 6 weeks later, then every 3 months. Average weight loss was 14.3 kg; average waist reduction was 11 cm.

Coffee may help prevent Atherosclerosis (hardening of the arteries)
http://www.ajcn.org/content/86/3/604.long - 10 healthy volunteers were given 200mL of Filtered coffee after an overnight fast; researchers measured the resistance of the volunteers' LDL to oxidation; LDL had increased resistance to oxidation, presumably due to increased incorporation of Phenolic acids (found in the Coffee) within the LDL particles.

Oxidation of LDL is considered to be a major initiating factor in the development of Atherosclerosis (hardening of the arteries), as can be read about here.